SARS Virus Treatments

Pandemic Survival

This eBook shows you what it takes to survive the next pandemic. There is no doubt that in the future, the world will be hit with a huge pandemic, either from natural causes or from a terrorist attack. As you look through history, you will be hard-pressed to find any pandemic in history that has killed less than 1 million people. You do not want you or your family to be among those millions. And with the help of the information in this eBook, you have a way to survive the global pandemic that will come. Wishing it won't happen doesn't do anything Preparing for it gives you the tools to survive AND thrive. This book contains the two-pronged approach of John Hartman's years of research in figuring out how pandemics work and living through a dangerous flu outbreak. This gives you the methods to both avoid getting a virus in the first place, and how to strengthen your immune system should you come down with a virus. You don't have to lay down and die. You can fight the next pandemic. More here...

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Lessons from the SARS Crisis

A final question can be posed what have the two governments learnt from the SARS crisis in terms of establishing a sound governance system During the SARS crisis, most criticisms were targeted at China due to its authoritarian political system. Nevertheless, we believe that every system can learn from such an unprecedented crisis, which has exposed the many cracks in the existing system. Specifically, the SARS crisis did lay bare the weaknesses of China's authoritarian system, but it also showed its strengths. Some of our contributors have objectively pointed out that every system has its own advantages and shortcomings. Apparently, both political systems have room for further improvement in order to be effective in coping with sudden social crises like SARS. Nevertheless, learning is a long process, and the process from the time the lesson is learnt to policy changes is even longer. Our contributors have found that all the relevant segments of society in both China and Hong Kong have...

Expression Profile Of Sarscov Subgenomic Rnas

We also detected some minor low molecular weight bands in some cases, possibly resulting from downstream AUG codons by leaky scanning. Cells transfected with subgenomic RNA8-GFP fusion construct displayed fair amount of fluorescence but in Western blot only a 27 kDa band of wild-type GFP was detected. Taken together-we showed that nine out of ten subgenomic RNAs could be functional messages in vivo however, existence of proteins encoded by these subgenomic in SARS-CoV infected cells is yet to be determined. In summary, ten subgenomic RNAs including two novel subgenomic RNAs (2-1 3-1) were identified in SARS-CoV infected cells by Northern blot, RT-PCR, and DNA sequencing. Nine out of 10 subgenomic RNAs were potentially functional messages in SARS-CoV infected cells. The initiator AUG codon of subgenomic RNA 8 (ORF8b) was inactive in our experimental set-up.

SARS and the Future of Chinas Political System

How will SARS affect China's political system We have discussed the immediate impact of SARS on China's politics from the top to the bottom. Many observers have argued that SARS will push the leadership to initiate greater political liberalisation and even democratisation. As we have discussed, the SARS outbreak has shown up weaknesses in Chinese political system and thus highlighted what could be done to reform the system. There has also been pressure from both domestic social groups and the international community for the leadership to initiate some reform to improve the level of governance in the country. In some sense, the SARS outbreak appears to have created an unprecedented opportunity for the Hu-Wen leadership to undertake reform initiatives. But the existence of conditions for political reforms does not necessarily mean that the leadership is prepared to or will initiate such reforms. In politics, there may not necessarily be a logical progression between prevailing...

Central Local Arrangements and SARS Management

The SARS outbreak and local management in 2003 provide us a vivid case of observing central-local relations at work in China. The belated and weak response of Guangdong government toward the disease in the early months illustrates three profound problems in the relations. First, information asymmetry hampers prevention of SARS. Localities enjoy an advantage over information regarding local situation, and the state keeps sensitive information away from the public. The center often relies on the locals in the localities to supply information of the same kind. The state is also reluctant to publicize highly infectious diseases out of the fear of public panic, social instability, economic downturns, and political consequences. Second, the center has no comprehensive and sensible way of evaluating local officials' performance. It relies too much on quantitative or mechanical indicators. Until recent years it pays heavy attention to the growth rate of local economy, and recently it has paid...

The Emergence Of Sars Coronavirus

Severe acute respiratory syndrome (SARS) was first described in November 2002, when inhabitants of Guangdong Province, China, presented with an influenza-like illness that began with headache, myalgia, and fever, often followed by acute atypical pneumonia, respiratory failure, and death. The outbreak spread over Asia, and to Europe and North America. A total of 8,096 cases were recorded, of which 774 (9.6 ) died.1-5 The etiological agent of SARS was identified as a novel coronavirus, SARS-CoV.6-10 This 2002-2003 SARS-CoV epidemic strain was successfully contained by conventional public health measures by July 2003.11, 12 SARS-CoV reemerged in Guangdong Province in the winter of 2003-2004, when it infected four individuals, all of whom recovered.13-15 No subsequent human-to-human transmission was observed in these latter cases. The infections in 2002-2003 and 20032004 were unlikely to be the first instances of SARS-CoV transmission to humans almost 2 (17 of 938) of serum samples...

Institutional Problems in Early SARS Management

Three problems characterized central-local relations in China. They were (1) information asymmetries in favor of the lower-level bureaucrats and against higher-level leaders and in favor of the state and against the public (2) mechanical and one-sided evaluation of cadres' performance and (3) fragmented bureaucratic authority. These three problems led to ineffective SARS management in the early months. During the SARS outbreak, national leaders also relied heavily on local officials for information, especially regarding the nature and effects of the disease. Vital information on SARS in Guangdong took quite a long time to reach the center, and its accuracy was reportedly questionable. In mid December 2002, two SARS patients sought treatment in Heyuan City. They infected eight medical workers. Around the New Year Day the Guangdong authority learned about the infectious disease. In early January, public health experts in Guangdong studied the disease in Heyuan and concluded that this...

The Commercialization of Healthcare Providers and the SARS Crisis

The increasing decline of the state's role in financing the health sector has resulted in the rapid commercialization of healthcare providers at almost all levels, leading to the surge in healthcare costs. As out-of-pocket finance is dominant, soaring costs would definitely drag down the utilization rate of healthcare services. The problem with SARS was that if SARS patients were reluctant or unable to receive treatment in hospitals, they would become infectors. Consequently, the utilization rates of healthcare services are on a decline. The updated data on utilization rates are not available, as the scheduled 2003 national health services survey was delayed due to the SARS crisis. From data collected in the previous national surveys conducted in 1993 and 1998 (see Figure 10), some observations can be made. The utilization of outpatient services in urban areas has increased The impact of the increasing commercialization of healthcare providers on the SARS epidemic is threefold. First,...

An Ailing Public Health System Exposed in the SARS Crisis

The most direct link between the increasing declining role of the state in financing the health sector and the outbreak of SARS is an ailing public health system. As a result of underinvestment from the state, many public 17 According to some overseas reports, some hospitals in Beijing attempted to conceal the number of SARS cases during the visit of the WHO inspection team. It is widely believed that the soaring number of SARS cases in Beijing after the sacking of Zhang Wenkang, then Minister of Health, and Meng Xuenong, then Mayor of Beijing, on April 20 was an indication of widespread concealment, although the Chinese authorities denied this. generate much revenue.23 In contextualizing the SARS crisis within the background of public health financing reforms, it would not be difficult to understand how such a public health system deemphasizing disease control could be terribly hit by the outbreak of a new disease. A more direct link between an ailing China's public health system and...

Animal Models For Sars

In 2002-2003, severe acute respiratory syndrome (SARS) was a newly identified illness that emerged in Southern China, spread to involve more than 30 countries, and affected more than 8000 people and caused nearly 800 deaths worldwide. Although the etiologic agent was rapidly identified to be a previously unknown coronavirus (named SARS coronavirus or SARS-CoV) and the outbreak was controlled by public health measures, no specific options were available for prevention and control of human disease. Over the past two years, a number of strategies for vaccines and immunoprophylaxis have been investigated. Animal models are essential for preclinical evaluation of the efficacy of candidate vaccines and antivirals, and they are also needed in order to understand the pathogenesis of SARS. A number of investigators around the world have evaluated several different animal species as models for SARS this effort is important for two reasons. First, because the source of SARS-CoV in the wild is...

Potential Uses Of Animal Models For Sars

As summarized above, mice, hamsters, ferrets, civets and several non-human primate species can support replication of SARS-CoV with or without accompanying clinical illness or pulmonary pathology. Each model has advantages and disadvantages (Table 2) but the common themes are that a number of animal species can be infected when SARS-CoV is delivered into the respiratory tract, the infection elicits a neutralizing antibody response and the animals are protected from subsequent infection. In comparing reports, readers should bear in mind that the virus used, inoculum and route of virus administration and age of the animal may represent important differences. In studies in mice, the age of the animals and use of anesthesia clearly affect the course of infection. The characteristics of each model should be taken into consideration in determining their utility and application. Table 3 lists potential uses of the models discussed above.

Severe acute respiratory syndrome SARS A

Severe respiratory illness that was first reported in 2002 in China, and quickly spread throughout Asia, North America, and Europe. Most of the U.s. cases of severe acute respiratory syndrome (SARS) occurred among travelers returning to the United States from other parts of the world with SARS. There have been very few cases as a result of spread to close contacts such as family members and health-care workers. Currently, there is no evidence that SARS is spreading more widely in the United states.

Structure And Dynamics Of Sars Coronavirus Main Proteinase Mpro

All protein functions required for SARS coronavirus replication are encoded by the replicase gene.1,2 This gene encodes two overlapping polyproteins (ppla and pplab), from which the functional proteins are released by extensive proteolytic processing. This is primarily achieved by the 34-kDa main proteinase (Mpro), which is frequently also called 3C-like proteinase (3CLpro) to indicate a similarity in substrate specificity with the 3C proteinase of picornaviruses.3 While useful at the time of initial description of the coronaviral enzyme, there are in fact large differences between the structures and mechanisms of these enzymes, making the designation of the coronavirus main proteinase as 3CLpro rather misleading. We will therefore use the term Mpro exclusively.

Sars Cov Why Susceptible To Monkeys

Despite rapid advances in our knowledge of SARS-Coronavirus (SARS-CoV), the regions of the virus spike glycoprotein and host receptor that are important for virus entry remain to be completely elucidated. The tropism of SARS-CoV for cells derived from many diverse species was analyzed by virus titration and by the use of a multiplex RT-PCR assay that differentiates input virus from virus that has entered a cell and initiated replication.1 Cells derived from monkey, human, and mink were shown to be productively infected by SARS-CoV. Interestingly, the level of virus produced varied dramatically (4 log10) between the susceptible cell lines. Human angiotensin-converting enzyme 2 (ACE2) was shown to have SARS-CoV receptor activity.2 Using conserved oligonucleotide primers and RT-PCR to amplify ACE2, we determined that the SARS-CoV susceptible cells expressed ACE2 RNA. We hypothesized that passage of SARS-CoV in cell lines expressing different levels of ACE2, or ACE2 from novel species...

How did the Lack of Information Worsen the SARS Crisis

Mirsky points out Communist China's long obsession with secrecy is one cause of the present SARS (severe acute respiratory syndrome) crisis. 12 The first SARS case took place in Guangdong in November 16, 2002. In the southern Chinese province of Guangdong (where SARS first appeared), the health department received a 'top secret' document from a government health committee on January 27 that contained disturbing information about a new pneumonia-like illness spreading in the region. 13 While Chinese leaders had access to top secret information about the outbreak of an epidemic, the general public knew little about it. An internal warning was issued within the local government on February 7 in Guangdong. However, cell-phone and Internet messages spread the news about SARS between February 8 and 11. The first local press conference about SARS was held on February 11, 2003 in Guangzhou. However, all information and even the discussion on the Internet were suppressed in late February in...

SARS and the Chinese Courts

It is well predicted that the next battlefield on SARS could be the court-room.42 Various and numerous cases will emerge from the SARS event. 39 See Cheng Jie. Prevention and treatment of SARS needs the exercise of power by people's congresses , at accessed on 26 Jul 2003. 40 See Li Yong and Wu Xiaoliang. SARS into the law , http www.iolaw.org.cn feidian shownews.asp id 954, accessed on 26 Jul 2003. 42 Courtrooms may become next SARS battleground , China Daily, 26 May 2003. They may include criminal, civil as well as administrative cases. The courts have already been handling such cases since the SARS outbreak. The Supreme Court and the Supreme Procuratorate jointly issued the judicial interpretation on applying certain laws for criminal cases resulting from the hampering of prevention and control of suddenly emerged infectious diseases on May 15, 2003. According to it, intentional spreading of infectious diseases is a crime of endangering public security and should be punished as...

Development Of Vaccines And Passive Immunotherapy Against Sars Coronavirus Using Mouse And Scidpblhu Mouse Models

We have investigated novel vaccines strategies against severe acute respiratory syndrome (SARS) CoV infection using cDNA constructs encoding the structural antigens spike (S), membrane (M), envelope (E), or nucleocapsid (N) protein, derived from SARS CoV (strain HKU39849, TW1, or FFM-1). As SARS-CoV is thought to infect the alveolar epithelial cell of the lung,in the present study, a type II alveolar epithelial cell clone, T7, was used to analyze the mechanism of CTL against SARS CoV membrane antigens. Mice vaccinated with SARS CoV (N) DNA or (M) DNA using pcDNA 3.1(+) plasmid vector showed T-cell immune responses (CTL induction and proliferation) against type II alveolar epithelial cells (T7) transfected with SARS (N) or (M) DNA, respectively. To determine whether these DNA vaccines could induce T-cell immune responses in humans as well as in mice, SCID-PBL hu mice were immunized with these DNA vaccines. PBL from healthy human volunteers were administered i.p. into IL-2 receptor...

Central Local Relations at the Second Stage of SARS Management

From early April onward, national leaders, especially Hu Jintao and Wen Jiabao, realized the increasing danger of mishandling SARS. They acted to mobilize the political machinery (the Party and the administration including public health agencies), social organizations, and the people to fight the disease. The center played up three instruments, injected new (even if temporary) dynamics into central-local relations, and eventually help turn secretive and low-profile SARS handling into open and effective management. 17 China admits underreporting its SARS cases , posted at http www.nytimes.com on 21 Apr 2003, accessed on the same day. As Huang (1996) suggested, the Chinese national authority retained its administrative control of cadres. At the second stage of SARS management, national leaders applied this reserved weapon to cope with the runaway epidemic. It ordered cadres to act forcibly on SARS, held them responsible for the outcome, and penalized ineffective senior officials. They...

SARS in Hong Kong

In their paper, Thomson and Yow explain how Hong Kong coped with the SARS crisis by looking at the role played by the government and civil society. They found that apart from the measures introduced by the Hong Kong government, the response of the Civil Society Organizations (CSOs) and the general public was crucial in halting the spread of SARS and reducing the fear, confusion and near hysteria at every level of society. To curb the spread of SARS, the Hong Kong government introduced a number of measures such as instituting screening procedures at immigration checkpoints, closing of schools, introducing quarantine measures and improving healthcare procedures. However, the government also committed a number of mistakes such as its delay in informing the public of the gravity of the situation, its indecision over the closure of the schools and failure to institute timely and adequate quarantine measures. Even before the SARS outbreak, the people of Hong Kong were already quite...

Sars In Animals

The epidemiological data of early SARS patients suggested that some of these index patients might have close associations with wildlife in Guangzhou.24 This prompted us to do a virus surveillance study in a wet market in Guangzhou. In this pilot study, evidence of SARS-like CoV infection were found in those samples collected from Himalayan palm civets (Paguma larvata) and a raccoon dog (Nyctereutes procyonoides)25 In particular, SARS-like viral isolates were recovered from civets. Genetic analysis of these viral RNA indicated the human and animals isolates are of 99.8 homology. These observations indicated the SARS-CoV in human might of animal origin. Our data also suggested the human virus might be a result of direct transmission from civets to humans. Subsequent serological and epidemiological studies in humans and civets confirmed this hypothesis. Interestingly, serological and virus isolation studies both indicated that the prevalence of animal SARS-CoV in civets from farms was...

SARS in China

The SARS provides a good example to show how different political systems respond and manage a sudden social crisis. This is especially true in the case of China given the country's size and complexity. In their paper, Zheng and Lye provide an in-depth analysis of how SARS spread from China to other parts of the world and how the Chinese government responded to the SARS crisis. Initially, China adopted a rather laid-back and disconcerting approach in coping with SARS. It was initially regarded as a purely medical issue which was thought to be best left to local governments or relevant central bureaucratic agencies to handle. It was only when SARS made its presence felt in other parts of the world and international pressures mounted that China began to put its act together. Nevertheless, Zheng and Lye also pointed out that it would be rather unfair to lay the blame for the spread of SARS squarely on China's failure to institute sufficient preventive measures. The SARS was an entirely...

John Wong and Zheng Yongnian

In the first half of 2003, severe acute respiratory syndrome (SARS) suddenly struck China and Hong Kong, claiming many lives and causing panic. It also jolted their economic growth, disrupted the social life of their citizens, and created much stress and strain on their political systems and governance. Like dealing with other external shocks , the management of the SARS crisis provides a good opportunity to examine the weaknesses and strengths of the political systems of China and its special administrative area, Hong Kong. Although both are Chinese communities, their political systems differ. China remains an authoritarian political system, despite the dramatic economic transformation that has occurred over the past two decades. Hong Kong inherited the British colonial political system with a rich tradition of rule of law and an efficient bureaucracy. Nevertheless, after its return to China, societal demands for greater democratization have increased. Given the different political...

Weaknesses of Chinas Political System

The dismissal of Minister of Health Zhang Wenkang and Beijing Mayor Meng Xuenong marked a major turning point in the Chinese government response to the SARS outbreak. By that time, SARS was no longer regarded as merely a medical problem to be resolved by the local governments as they deemed appropriate but had become a political issue that called for a concerted national response. It took a while for this change of perception to occur. Why did the central government not get into the act earlier to contain the outbreak There are several reasons for this delayed response each of which will be examined below. The first reason has to do with the economic and political dynamics of Guangdong. As mentioned, local newspapers in Guangdong did initially carry reports on the SARS outbreak. But why did the Guangdong provincial government decide to impose a media gag There were political and economic actions behind its actions. From the economic perspective, Guangdong, being the biggest trading...

Responding to External Pressure

The strength of China's political system could also be seen from its ability to make a complete change mid-way to deal head-on with the criticism levelled both internationally and domestically on China's lack of information provided and slow response to the SARS outbreak. Much of this change could be attributed to the changed perception towards the SARS outbreak held by the top leadership. Given China's weak institutional and legal framework, the role of the top leaders and their perception of the problems confronting the country would assume even greater importance. Once it was decided that it was no longer in China's interest to ignore the views of the international community and its own public, they began to react to contain the damage. initially, the regime adopted a non-cooperative attitude towards the World Health Organization (WHO) eager to conduct field trips to China to better understand the extent of the SARS outbreak.46 It was also not receptive to comments from other...

The Implementation Dilemma

SARS originated in Guangdong Province, China. It was reported that the first SARS case was discovered there as early as November 2002. China was blamed for the spread of SARS to the rest of the world by its mismanagement at the early period of the outbreak. One of the reasons behind the mismanagement is apparently the failure of the relevant Chinese law enforcement. The 1989 Law and related measures should have applied to the SARS case from the very beginning when SARS emerged since they were designed to combat infectious diseases. It should be pointed out that though SARS was a new disease beyond human knowledge and its initial symptoms looked like flu, even if it was regarded and treated as a kind of flu at the beginning, it should be governed by the 1989 Law which lists flu under Category C of infectious diseases.7 Unfortunately, the Law was forgotten and or ignored at that time. It was mentioned only once at a press conference by a high-rank official from the government health...

Medical Insurance Inequality and Public Health Insecurity

One of the most significant factors characteristic of the current Chinese healthcare regime is the lack of universal medical insurance coverage. Many uninsured SARS patients were very reluctant to pursue treatment until they were in severe sickness. As a result, they had already become infectors, super- or not, when they had to receive the treatment. The failure of receiving early treatment was one of most important factors for the spread of the SARS virus among the crowd. The uninsured normally does not seek medical treatment promptly when they are getting ill, in particular when they feel that their illness is not severe.8 One of the important factors contributing to the SARS epidemic is that during its early stage, its symptoms were widely misper-ceived as flu and therefore patients did not take them seriously. There were indications that the uninsured was reluctant to seek early treatment when they had SARS-like symptoms until the situation worsened. An incomplete statistical...

Temporary Measures and Longterm Commitments Towards a More Active Role for the State

As the ailing healthcare system could not handle the SARS crisis, the Chinese government eventually stepped in to restore many measures prevalent in the old regime. The virtue of social mobilization and control with authoritarian and even totalitarian characteristics were rediscovered. In brief, the government's intervention fell into the categories as follows 26 24 According to some reports, many doctors in Beijing and Taiyuan knew little about SARS or the possibly feasible treatments used in Guangdong when the first batch of SARS patients was received. As a result, the number of SARS cases in hospitals and especially among healthcare professionals soared. See Investigating SARS , pp. 110-113. 25 This phenomenon of institutional fragmentation was openly criticized by some WHO officials at a news conference held on April 16, 2003. See Investigating SARS , p. 35. 26 The following is summarized from a speech delivered by Gao Qiang, Deputy Minister of Health to the International...

Publication and the Advance of Knowledge

The Chinese scientific and medical community seems to disagree with Yang Huanming's sensational argument that Chinese scientists were defeated by SARS. One piece of evidence they would present is China's low mortality rate among SARS patients. According to the WHO statistics, the cumulative mortality rate related to SARS is 9.6 , but would be significantly high at 15.3 if not the low mortality rate in China, which is only 6.5 , were excluded (Table 1). The statistics seem to suggest that China has been quite successful in treating SARS patients at the clinical level, which has in turn made significant contributions to the reduction of death from the disease worldwide.33 In other words, the cumulative 31 Qin E'de. et al. A complete sequence and comparative analysis of a SARS-associated virus (Isolate BJ01) , Chinese Science Bulletin, Vol. 48, No. 10 (2003), pp. 941-948. 32 Li Yuanli. Why did China lose in the SARS research (in Chinese), China Business News, 9 Jun 2003. 33 Ironically,...

Post Crisis Efforts and Persistent Problems

In mid-April, when the international pressure accumulated, China's political leadership started to take note. The Party General Secretary Hu Jintao inspected the Guangdong CDC and the Premier Wen Jiabao convened a State Council meeting to discuss the establishment of a national mechanism to deal with the public health emergency. On April 20, China finally lifted the restriction on the publicity of SARS, removed the health minister and the Beijing mayor from their positions for their inability in handling the crisis, and mandated further sanctions to those who failed to report the SARS cases. On the same day, President Hu inspected the CAMMS and the BGI, boosting the morale of the 41 Xiao Qiao. SARS in China , sars_jinian.txt, accessed on 23 Aug 2003. scientists at the frontier of the SARS research. In the meantime, as the epidemic spread, attracted more press coverage, and generated more effective lobbying from the scientific and medical community, the commitment to the aliment...

Chinese Authoritarianism and Information Control System

China is not devoid of a mass communications system. By the end of 2002, China had 2,137 newspapers, 9,029 journals, 306 radio stations, 368 television stations, 1,526 wire broadcasting and television stations at county level, and 568 publishing houses. It is amazing thus that except for a few days in February 2003, there was no report on SARS during the early stages of the outbreak despite such a gigantic network of newspapers, journals, radios and television stations. The Party-State was so powerful that it was able to tighten up its control over the media through the following mechanisms and measures in 2002 when China was evaluated by Freedom House as not free country (see Table 1). 10 Zhang Erping. SARS Unmasking censorship in China , China Rights Forum, No. 3, 2003, p. 47.

Closing a Window of Opportunity

From April-July 2003, the Propaganda Department of the Party maintained tight control over how the campaign against SARS was reported and clearly preferred the old ways. The party was controlling information about the virus more closely than ever, and as for political change, SARS was not bringing it. 27 The official media had cast the party as the bulwark in the unfolding crisis.28 The government criticized and warned against several journals and newspapers such as Southern Weekend that were very aggressive during the crisis. A propaganda official who suppressed media coverage of the outbreak in Guangdong was appointed editor of China's most liberal newspaper, Southern Weekend. This highlighted the party's determination to keep a tight grip on the press. The Propaganda Department still banned reports of Japanese sex-seeking tourists in Zhuhai after September 28, 2003 and on AIDS in Henan in October 2003. Unwarranted descriptions and rumors contributed to the greater fear of SARS....

Why didnt the Chinese Government Learn a Lesson Suggested by Liberal Intellectuals

Chinese liberal scholars think that the controlling and concealing of information by the Chinese government contributed to the outbreak of SARS. Chinese leaders however think otherwise. They are of the opinion that some of the more effective and successful measures against SARS are mobilization, socialist spirit , the use of law, tough social control, and even the application of brute force. China's political system proves to be resilient, cushioning the impact without substantial change in the area of the freedom of press. The success of the Party State in the campaign against SARS indeed encourages it to draw different lessons. In a seminar on public health and economic development on June 17, 2003, Premier Wen Jiabao summarized the lessons that have been learnt from the SARS crisis pay greater attention to and improve public health system enhance the governmental capacity of handling an unexpected crisis devote much more attention to the management of society and attach importance...

Problems with the Governments Response

The Hong Kong government's success in handling the SARS outbreak can be measured in terms of (1) the number of people afflicted by the disease and the speed at which its spread was halted and (2) governmental mistakes and incohesive action. 10 Cathy Chan. SARS helps widen Hong Kong deficit , International Herald Tribune, 1 Sept 2003. Figure 1. Deaths from SARS in Hong Kong as of June 2003 Source SARS updated charts and figures in Hong Kong , Hong Kong University of Science & Technology, at Figure 2. Officially Confirmed SARS Patients in Hong Kong as of June 2003 Source SARS updated charts and figures in Hong Kong , Hong Kong University of Science & Technology, at The virus reached every corner of the Territory. At its peak, on April 14, as many as 176 buildings were identified with confirmed SARS cases (see Figure 3). Each of these cases was hospitalized for treatment.12 The worst affected areas were the districts of Kwun Tong in Kowloon, and Shatin and Taipo in the New Territories....

Significance of the Crisis

SARS was an external shock that was completely unpredicted. Not surprisingly, the eventual emergency response of the government was as in a war, i.e., the government measures were inherently undemocratic, and there were bound to be mistakes. SARS caused cracks to appear in the functioning of all the healthcare delivery systems and administrations around the world that suddenly had to cope with it. It is fair to say that In the initial stages, none of the health professionals in Hong Kong knew what they were dealing with. Moreover, according to recent statistics, there had been up to 1,400 cases of pneumonia admitted into Hong Kong hospitals per month.25 There had also, for some time, been various strains of avian flu appearing in the region. It took some weeks before the international medical authorities reached agreement on what were the classic symptoms and means of transmission. It was difficult for any government to offer clear instructions. Although there was no doubt that...

Hong Tao Chinas National CDC and the Chlamydia Hypothesis

In November 2002, the first case of a mystery illness occurred in Guangdong province, which caused a severe panic during the Chinese New Year of 2003. On February 11, 2003, the Guangdong Health Bureau held the first press conference on the matter in Guangzhou, the capital city of Guangdong, disclosing that there had been 305 cases of a mystery aliment with five deaths in the province. According to the health officials, the provincial and national centers for disease control and prevention (CDC) had ruled out the possibility that the disease is anthrax, plague, or bird influenza. During that press conference, Dr. Zhong Nanshan, director of the Guangzhou Institute of Respiratory Disease affiliated to the Guangzhou Medical College and a prestigious member (yuanshi) of the Chinese Academy of Engineering (CAE) who would later be known to the world for his role in combating SARS, named the disease atypical pneumonia which was most likely caused by a virus.4 Also on that day, the first SARS...

Zheng Yongnian and Lye Liang Fook

The outbreak of the severe acute respiratory syndrome (SARS) and efforts to contain it have posed what is generally regarded as the first major political test to the Hu Jintao-Wen Jiabao leadership since they took over the helm of the party and government. The coronavirus that supposedly originated from the small municipality of Foshan in Guandong Province soon spread uncontrollably to other provinces in China and even abroad. The political fallout from its tenacious spread took the leadership by surprise and showed up weaknesses in China's political system. The SARS outbreak has again turned the spotlight on China's political system. An examination of how this system has handled the SARS outbreak will not only give us an idea of how the regime has faired in the midst of the challenges posed by the new environment, i.e., globalization, market economy and social mobility, but also some sense of the direction the Chinese political system is likely to head. This paper is divided into...

Administration by

Right to presentation and explanation, the right to apply for administrative review or launch an administrative litigation. The new law explicitly forbids government agencies from empowering themselves with the right to grant permits or collecting fees not required by law. Through the implementation of the Law, the amount of administrative licensing will be greatly reduced and departments under the State Council will no longer have the right to determine whether a certain economic activity needs an administrative permit. While the Law has been hailed as a great help in China's efforts to build a market economy and check corruption ,29 its implementation will meet a series of challenges. First, the Law only provides general principles which result in ambiguities and would turn the law into an un-enforceable dilemma in practice. Second, the advanced legal spirit embodied in the Law may not be endorsed by the government and its officials who have such administrative power in hand for a...

What Lessons Should the Chinese Government Learn According to Liberal Intellectuals

In the aftermath of the SARS crisis, Chinese intellectuals demanded more open reporting and accountability. Xu Jilin argues If a society faced with a crisis can only passively depend on government control, this in itself represents a latent crisis. 35 Putting people's interests first should be translated into a more liberal political system. A critical lesson from the SARS crisis is that people have the right to access information, the right to know (zhiqingquan). SARS linked the right to know with people's health. The victims, the families, and the public have the right to know the inside story. As Fewsmith argues By challenging the Chinese to consider not only the accountability of their government, but also issues of openness, trust, responsiveness, and the 'right to know', the SARS crisis seems likely to provide a major impetus to new thinking about relations between society and state. 36 Zhang Shuguang, an economist, advocated that news control system be abolished and the freedom...

Strengths of Chinas Political System

The SARS outbreak has the tendency to show up weaknesses in the Chinese political system and underestimating its strong points. There are positive aspects of the Chinese political system in combating the SARS outbreak that are worth highlighting here. The most notable of which is that once SARS became a political issue and became an item on the national agenda, the top leadership accorded the highest priority to combat SARS. National resources were mobilized to deal with the outbreak. To a large extent, the authoritarian nature of the Chinese political system enabled the top leadership to implement quite effective measures to bring SARS under control.38 Once the top leadership decided that an all-out national effort was necessary, it moved quickly. The party made the first move and the government followed soon after. The Politburo Meeting chaired by Hu Jintao on April 17, 2003 on SARS was the first public indication that the top leadership was getting its act together. Three days...

Meeting International Standards

The main and specific international law regulating infectious diseases, in particular SARS, is the International Health Regulations (IHR) which was adopted in 1969 and entered into force in 1971.54 China was one of the original members of WHO and signed the WHO Constitution on July 22, 1946. The seat in WHO was occupied by the representative from the Republic of China (ROC) until 1972 when the People's Republic of China (PRC) notified the WHO Director-General to participate in the WHO activities. This transfer of representation was a result from the transfer of the United Nations seat to China.55 Accordingly, the PRC notified the WHO in May 1979 of its recognition of the IHR which should legally bind the PRC as from June 1, 1979.56 travelers, deratting, disinfecting and disinsecting of transport vehicles and health measures at airports and seaports. It defines the terms such as disinsecting , epidemic , health administration , health authority , imported case , infected area ,...

The Economic Impact

The SARS not only caused hundreds of lives, but also affected different economies. In their paper, Wong, Chan and Liang give an overall view of the economic impact of the SARS. They found that the impact operated like a cyclical phenomenon, disrupting economic growth much akin to a business cycle affecting both the demand and supply sides in the short run. The demand shock to the economy was reflected by a fall in consumption. From the supply side, the SARS disrupted production and business operations, which adversely affected the services, particularly the travel industries, and certain manufacturing industries in the SARS affected region. Trade was also hampered, aggravating the supply-side shocks. The negative external shock of SARS further manifested itself through the financial markets, as market confidence weakened and stock prices fell. Apart from the cyclical effects , the SARS crisis also exposed or perpetuated the structural weaknesses of the economies, for instance, the...

Overview

The recent SARS outbreak struck the Greater China economies as primarily a random and unforeseen event. The impact operates like a cyclical factor, disrupting economic growth through both the demand and supply sides in the short run. The demand shock to the economy is reflected by a fall in consumption. From the supply side, SARS disrupts production and business operations. This will adversely affect both the services and manufacturing sectors. Delays in international shipments of inputs and final commodities may also be experienced as trade is hampered, aggravating the supply-side shocks.1 The negative external shock of SARS also manifests itself even faster through the financial markets. If the SARS outbreak cannot be effectively contained, fear of the disease may continue to grow, weakening market confidence and depressing stock prices. The wealth effect of these could further aggravate the demand-side shocks. The external shock arising from the SARS outbreak therefore impacts the...

Taiwan

Taiwan's economy was already slowing down before SARS due to the US recession and global slump in electronics exports. The SARS-induced downturn however proved short-lived for Taiwan's economy and most of the return to growth was cyclical. In the first quarter of 2003, the economy continued to grow at a rate of 3.5 but contracted by 0.1 in the second quarter due to the outbreak of SARS (Figure 10). It grew 4.2 year-on-year in the third quarter and is estimated to expand 4.7 in the fourth quarter. As the economy steadily recovers from the impact of SARS, the official growth rate is forecasted to be 3.2 for 2003.16 The initial impact of SARS is felt on the services sectors. According to a report by the Cabinet's Council of Economic Planning and Development, tourist arrivals to Taiwan in April reportedly fell by 50-60 compared to the same period last year and hotel occupancy dropped by more than 30 (refer to Table 1). Domestic tourism is expected to be badly hit and is estimated to fall...

New Regulations

Significantly, following the announcement, China enacted new regulations on public health emergencies in May 2003, the first of its kind in China.12 The Regulations aim to establish a prompt and effective emergency response mechanism and enhance the government's ability of handling public health emergencies such as SARS. Public health emergency is defined as serious infectious diseases, massive unknown diseases, serious food or vocational poisoning, which suddenly happen and cause or possibly cause serious damage to public health, and others which seriously affect public health.13 The Regulations establish the emergency information publicizing system as well. During the SARS period, the information on SARS was publicized every day. The new regulations can be regarded as an extension and update of the 1989 Law since it elaborates on and further specializes the relevant provisions in that Law. For example, Article 30 of the 2003 Regulations provides the procedure of declaring statutory...

Concluding Remarks

What lies ahead is the need to revise the 1989 Law which proved inadequate in its enforcement during the anti-SARS campaign. For example, 62 See WHO. Severe acute respiratory syndrome (SARS) Status of the outbreak and lessons for the immediate future , Geneva, 20 May 2003, p. 7. the Law does not have any clear provision on whether a hospital has the right to refuse to take in patients of infectious diseases. Such refusal happened during the early SARS period. Second, there is no provision on legal liability imposed on those patients who refuse to be quarantined.65 It is reported that the revision of the 1989 Law has been put on the legislation agenda in the NPC.66 Other related laws also need necessary revisions due to the SARS factor. For example, the Law on the Protection of Wildlife, which is linked to the prohibition of eating wild games such as civet cats. It has been also targeted as one of the laws to be revised in the NPC legislation plan.67 China openly acknowledged that it...

Cao Cong

* Fieldwork for this paper was supported by a research grant (R348-000-005-112) from the Faculty of Arts and Social Sciences, the National University of Singapore. The revision of the essay has benefited from the comments made by participants at SARS and Governance in China, a workshop held at the East Asian Institute, the National University of Singapore, and by Professors Jonathan R. Cole and Richard P. Suttmeier. 1This is a remark made by Yang Huanming, director of the Beijing Genomics Institute (BGI), then a non-governmental research institute, that would become part of the Chinese Academy of Sciences amid the SARS episode, reportedly to Hu Jintao, the general secretary of the Chinese Communist Party Central Committee and China's state president. See Xie Xiang and Zhou Xinyu. Yang Huanming's pain (in Chinese), China Youth News, 26 May 2003. The crisis of severe acute respiratory syndrome (SARS) between the winter of 2002 and the summer of 2003 in China was a serious test for its...

Sequencing

As the above narrative indicates, between mid-February and mid-April, at least three groups of chinese scientists were working on the pathogen-esis of SARS the Zhu Qingyu group at the CAMMS, the Hong Tao group and the Li Dexin and Bi Shengli group at the Chinese CDC. In the 16 Zhang Wenkang, then the health minister with training in medicine, presumably knew that chlamydia is no big deal, which explains why he dared to conceal the SARS outbreak (interview, Beijing, China 3 Dec 2003). meantime, a few Chinese biologists also tried to get the tissue samples from deceased patients, whose main interest was to sequence the genome of the SARS-causing virus. The following discussion will focus on one of the genome research powerhouses in the world the Beijing Genomics Institute (BGI). The BGI was a product of China's participation in the International Human Genome Project (IHGP), the interests of a group of Chinese life scientists working overseas, including Yang Huanming and Wang Jian, to...

Conclusion

Although SARS occurred first in China which also had the most cases, scientists and physicians from mainland China have failed to capitalize 46 Lawrence K. Altman. China lags in sharing SARS clues, officials say , The New York Times, 5 Aug 2003. 47 David Cyranoski. SARS triggers biomedical shake-up in China . on their advantages and resources. The SARS outbreak has revealed serious shortcomings of the China scientific and medical community to respond to emerging diseases. Were these the problems of individual scientists, of institutions, or of culture Although science is competitive in nature, it could become cooperative, especially when parties involved could tackle a problem quickly through the division of labor, or from different perspectives, when scientists in a nation work together amid international competition, and when there is an emergency that calls for the combined endeavor of the scientific community. This time, China's scientists could definitely turn the SARS crisis to...

Managing the Crisis

4 Hong Kong's SARS whitewash , Asian Wall Street Journal, 7 Oct 2003, p. A 11. 5 See World Health Organization (WHO) website http www.who.int csr sarsarchive 2003_04_02 en , Oct 2003. Hong Kong was finally removed from the WHO's list of SARS infected areas on June 23 after 20 days had passed without any fresh outbreaks in the Territory. On March 29, all of the Territory's immigration control checkpoints adopted health-declaration procedures. The Department of Health stationed officers at each checkpoint to check if anyone coming into Hong Kong showed signs of atypical pneumonia. Starting from April 17, passengers leaving the Territory by plane had their temperatures taken before they checked in for their flights. If they were found to have a fever, they would be asked to see a doctor at the airport at their own expense who would determine the possibility of their suffering from SARS. 7 Eventually, 329 residents of Amoy Gardens became infected and 42 died. SARS Expert Committee Report,...

Public Response

Long before the SARS outbreak, many Hong Kongers were expressing great disappointment with their government which is executive-style, not popularly elected. Currently, only 24 members of the 60-seat Legislative Council are directly elected, and of the remaining seats, 30 are elected from professional or occupational constituencies and six by an 800-strong pro-Beijing Committee. Thus, with the support of lawmakers from the pro-business Liberal Party and the pro-Beijing Democratic 21 Patsy Moy. Hospital is scolded for keeping SARS cases quiet , South China Morning Post, 3 Jun 2003. The Asian financial crisis which began soon after the British Government left in 1997, had devastating effects on Hong Kong especially. The city had always prided itself on virtually no unemployment, and it suddenly found itself with a rate above 8 . In the following year, a frightening outbreak of avian flu occurred, and there were numerous questionable pronouncements pertaining to right of abode. The...

Hong Kong

Statistics Sars Hong Kong

The SARS outbreak could not have come at a worse time for Hong Kong, whose economy was already facing a serious recession with rising unemployment and low growth. As seen from Figure 15, unemployment was at a high of 7.8 in 2002 while economic growth was only 2.3 in the same year. With the spread of SARS in mid-March 2003, Hong Kong's economic woes were further exacerbated. In the second quarter of 2003, real GDP contracted by 0.5 , down from an increase of 4.5 in the first quarter (Figure 16). Economic growth rebounded in the third quarter and grew 4 from a year earlier,20 as consumption witnessed a pickup due to a rise in PRC tourists as a result of relaxed travel rules for Guangdong residents. Recent government forecast for 2003 is estimated to be at 3 (from the previous forecast of 2 ), the second revision in two months to reflect the rapid recovery from SARS. Among the Greater China economies, HK's tourism-related services including airlines, hotels, restaurants, entertainment...

Proteases And Proteolytic Processing

The N-terminal regions of the coronavirus polyproteins' which are poorly conserved among the coronavirus groups I, II, and III, are cleaved at two (in IBV) or three sites (in all other coronaviruses) by one (IBV and SARS-CoV) or two zinc-finger-containing papain-like cysteine proteases called PL1pro and pL2pro.24-32 PLpro cleavage sites are usually flanked by small residues (mainly Gly and Ala).15 PL1pro and PL2pro probably evolved by gene duplication in one of the ancestors of the present-day coronaviruses.29 For MHV, it was recently demonstrated that cleavage of the nsp1 nsp2 site and, even more suprisingly, the C-terminal nsp1 and the entire nsp2 sequence are not required for MHV replication in vitro.33-35

Swimming in a Sea of Microbes

Patients in a Singapore hospital wait to be tested for SARS. The SARS virus was the first new disease-causing organism to be discovered in the twenty-first century. Patients in a Singapore hospital wait to be tested for SARS. The SARS virus was the first new disease-causing organism to be discovered in the twenty-first century. remote village in China. Researchers may never know how or why the paths of man and microbe crossed, but that fateful event led to the global outbreak in 2003 of SARS (severe acute respiratory syndrome). Health officials do know that the doctor traveled to Hong Kong, infecting many of the guests on the ninth floor of a four-star hotel. One of those guests left the hotel and boarded an overseas flight to Toronto, Canada. Along with her luggage, she carried with her the SARS virus. The microorganism proved to be an eager traveler. It unwittingly hitched rides inside its victims to Taiwan, Singapore, Vietnam, and dozens of other countries. In reaction to this...

Materials And Methods

Deletions of the nsp2 coding sequence were engineered into the infectious cDNAs of MHV and SARS-CoV by deleting nt 951-2705 (aa Val248-832Ala) for MHV and nt 805-2718 (aa Ala181-818Gly) for SARS-CoV. Mutant viruses were then generated as previously described.1,2 Vero-E6 cells were infected with SARS-CoV at an MOI of 1 PFU cell. At 12 h p.i., cells were harvested and lysates resolved by SDS-PAGE. Separated proteins were transferred to nitrocellulose, and nspl, nsp2, nsp3, and nsp8 antibodies were used to detect viral proteins as described.3

Results And Discussion

The deletion of the nsp2 coding sequence from both MHV and SARS-CoV yielded infectious virus. Retention of the engineered deletion was confirmed by sequencing of viral RNA from progeny viruses as well as by detection of viral proteins from infected cells by immunoprecipitation (MHV, Fig. 1) and immunoblot (SARS-CoV, data not shown). No additional mutations were noted in the regions sequenced, consisting of bases 500 nt 5' and 3' of the deletion for MHV and 250 nt 5' and 3' of the deletion for SARS-CoV. To determine if the deletion of the nsp2 coding region altered processing within the replicase polyprotein, MHV-infected cells were radiolabeled with 35S -methionine cysteine, lysed, and viral proteins were detected by immunoprecipitation (Fig. 1). While MHVAnsp2 mutant virus produced no detectable nsp2 protein, all other tested proteins (nsp1, nsp3, and nsp8) were processed comparably to wild type, demonstrating that deletion of nsp2 from the viral polyprotein did not inhibit...

Identification Of Novel Subgenomic Rnas

Northern blot, RT-PCR, and DNA sequencing revealed the existence of ten subgenomic RNAs including two novel subgenomic RNAs named 2-1 and 3-1. The leader-body fusion site (ACGAgC) of subgenomic RNA 2-1 has one nucleotide mismatch (lowercase) with SARS-CoV leader core sequence (CS-L ) ACGAAC and is located inside the S gene, 384 nucleotides downstream from the authentic CS (ACGAAC) for mRNA 2 S. The second novel subgenomic RNA (3-1) corresponded to the 3b ORF that was predicted to be expressed from mRNA 3. The leader-body fusion site (AaGAAC) for subgenomic mRNA 3-1 is 10 nucleotides upstream of AUG start codon of ORF 3b and has a mismatch (lowercase) with the SARS-CoV leader core sequence (ACGAAC).

Chlamydial pneumonia See pneumonia

For centuries cholera thrived only in northeast India, where outbreaks still occur regularly, but as the world trade routes opened in the 1800s, cholera became pandemic, spreading throughout the world and killing millions of people in a series of epidemics. It was London physician John Snow who correctly identified sewage-contaminated drinking water as the source of the epidemic of 1853-54. In his research, he compared the incidence of cholera in a neighborhood with two different sources of water, one of which was contaminated with sewage. cholera-infected bilgewater into the Lima harbor. The bacteria contaminated the fish and shellfish, which Peruvians ate raw from there the bacteria got into the sewers and from there into the water supply. The disease then spread throughout south and central America where the epidemic continues to this day. The particular bacterium responsible for the pandemic El tor (V. cholerae 01) can survive in water for long periods. By September 1994 more than...

Discussion And Conclusion

In this study, we identified Ubc9 as a host protein that interacts specifically with SARS-CoV N protein. This interaction was verified both in vivo and in vitro. Furthermore, we showed that, in addition to phosphorylation, the N protein was modified by covalent attachment of SUMO to its lysine 62 residue. Evidence provided demonstrated that sumoylation may promote homo-oligomerization of the protein. Recent studies have shown that the C-terminal one-third region is essential for self-association and multimerization of the SARS-CoV N protein.4,12 Data reported in this study demonstrate that sumoylation of the SARS-CoV N protein dramatically enhances the homo-oligomerization of the protein. Promotion of oligomerization of protein by sumoylation has been speculated for a pathogenic protein, Huntingtin.13 Because self-association and homo-oligomerization of N protein are essential for the assembly of nucleocapsid core, it suggests that sumoylation would play an important role in the...

Avian erythroblastosis virus See avian leukaemia virus

Avian flu Avian influenza, bird flu A highly contagious strain of influenza that affects poultry and can be transmitted to humans having switched species it could become extremely virulent (a similar phenomenon occurred with the 1918 strain of flu, which caused more deaths than the preceding 4 years of war). The H5N1 strain is currently causing considerable concern.

The Role Of E Protein

The CoV E protein is a small polypeptide ( 10 kDa) that is only a minor constituent of virions. Nevertheless, it profoundly affects both VLP and virus assembly. E protein sequences diverge widely across the three CoV groups, but all CoV E proteins have the same architecture a short hydrophilic amino terminus, followed by a large hydrophobic region, and a hydrophilic carboxy-terminal tail that constitutes one-half to two-thirds of the molecule (Fig. 4). Investigations with both the MHV and IBV E proteins are in agreement that E is an integral membrane protein and that its carboxy-terminal tail is cytoplasmic (corresponding to the interior of the virion).20,44 Moreover, for IBV E, the carboxy-terminal tail alone can specify targeting to the budding compartment.45 The disposition of the amino terminus is less clear, however. A lumenal (or virion-exterior) topology has been inferred for the IBV E protein amino terminus, based on its inaccessibility to antibodies at the cytoplasmic face of...

Particle Characteristics

Particles of SARS-CoV, FIPV, and MHV were prepared from Vero-E6, AK-D, and DBT cells, respectively. MHV and SARS-CoV were also produced in cells cultured with tunicamycin, to form spike-depleted particles with low infectivity. For safety reasons, all particles were fixed with 10 (for SARS-CoV) or 1 (for FIPV and MhV) formalin in pH 6.5 HEPES-buffered physiological saline before imaging. All viruses were collected by sucrose gradient ultracentrifugation, and each remained highly infectious until fixed. Each virus appeared approximately round in cryo-EM images, with a fringe of spikes protruding from the viral membrane and a region of lower density near the virion center (Fig. 1A-B). The average diameter of the membrane-enclosed part of each virus was similar, ranging from 830 A for SARS-CoV to 960 A for FIPV (Fig. 1C). The diameters of MHV and SARS-CoV virions were distributed more tightly than diameters of FIPV or spike-depleted, tunicamycin-grown MHV. The mean diameters of native and...

Viral Ribonucleoprotein

Preparations of each virus contained a small amount of material that was consistent with the appearance of Coronavirus ribonucleoprotein (RNP).18 A particularly interesting image of a SARS-CoV particle trapped in a partially uncoated state at the time of freezing (Fig. 3A-B) shows the spiral RNP partially uncoiled from an approximately round RNP core. The RNP proximal to the extruded membrane segment remains roughly spherical, and appears to be connected to the inner face of the membrane at the ruptured fringe (Fig. 3C).

Golfers elbow See epicondylitis

Goodpasture's syndrome This is a rare, life-threatening autoimmune illness that causes lung hemorrhage and kidney failure. Ernest W. Goodpas-ture (1886-1960) first described the illness in 1919 when he was examining the lungs of patients who had died in the 1918-19 influenza epidemic and noted a new illness that affected the lungs and kidneys of one patient. In 1958, almost 40 years later, M. C. Stanton and J. D. Tange attached the name Goodpasture's syndrome to an illness that caused severe lung and kidney disease. In subsequent years

Coronavirus S Proteins And Their Receptors

Three distinct genetic and serological groups of coronaviruses have been defined.28, 29 Coronaviruses from groups 1 and 2 are known to cause disease in humans.30 Human coronavirus 229E (HCoV-229E), a group 1 virus, and human coronavirus OC43 (HCoV-OC43), a group 2 virus, cause mild upper respiratory infections that result in self-resolving common colds in otherwise healthy individuals.29, 30 Human coronavirus NL63 (HCoV-NL63 also referred to as HCoV-NH and HCoV-NL) has recently been identified as a group 1 virus causing conjunctivitis, croup, and sometimes serious respiratory infections in children.31-33 HCoV-NL63 is also notable for its use of the SARS-CoV cellular receptor ACE2 to infect cells.34 Another group 2 coronavirus (HCoV-HKU1) was recently isolated from a 71-year old man with pneumonia.35 SARS-CoV and SARS-CoV-like viruses found in animals also cluster with group 2 viruses, although they are outliers of group 2 and have been also described as group 4, or, more recently,...

Trypsin Mediated Proteolysis Of S Protein

The precise requirement and role of glycoprotein processing for coronavirus entry and membrane fusion is not well defined. Many coronaviruses, such as mouse hepatitis virus (MHV), contain a furin cleavage site within S that yields S1 and S2 subunits 10,11 This site, however, is not absolutely required for infection, although lack of cleavage lowers S-mediated cell-cell fusion.11 In contrast, SARS-CoV S, both when overexpressed in cells, and on mature virions, is predominantly in a full-length, unprocessed form (Fig. 1A, left-hand lane). However, cell-to-cell fusion mediated by SARS-CoV S was enhanced by pretreatment of effector cells with trypsin.9 Thus, the role of proteolysis of SARS-CoV S by trypsin-like proteases in cell-free virus infection was examined. Lentiviral-based pseudovirions incorporating SARS-CoV S into their lipid coats9 were produced in 293T cells virions termed HIV(SARS-CoV S) . Analysis revealed that following pretreatment with trypsin, a C-terminal fragment of...

Geographic variation 199

Geographic areas of affinity (GAA) A framework to facilitate tracking of the HIV AIDS pandemic, analyze its impact, and monitor the response Despite its utility, it is important to note that the GAA system is still based on generalizations and assumptions. The present delineation of the 10 GAAs is therefore only intended as an interim classification. The Global AIDS Policy Coalition (a coalition and committed to tracking the evolving HIV AIDS pandemic, critically analyzing the global response and encouraging policy analysis and advocacy activities) is commissioning work to develop a more sophisticated classification system which will seek to take into account an even broader range of relevant factors. Their goal is to understand the local, national, and regional features of the pandemic, information critical for generating a more robust and focused global response. geographic distribution HIV AIDS has reached every part of the world. Its extensive spread started in the mid- to late...

Ggcctctagattatgtgtaatgtaatttgacacccttgag

3400 nucleotides and the 1200 bp PCR product were ligated in the pCG1 vector via restriction sites BamHI and Pstl. The new plasmid was designated TGEVS-pCGl (Fig. 1). For the generation of mutant Y1440A-pCG1, the respective pTMl construct was digested with Spel (restriction site at position 3834) and Pstl. The resulting fragment was inserted into TGEVS-pCG1 via these restriction sites (Fig. 1). The 3'-end of the SARS-CoV S protein was amplified from the plasmid pcDNA-spike (kindly provided by Dr. Deng) by PCR using oligonucleotides c and d (see Table 1, Fig. 1). Primer d contained an Xbal restriction site. After incubation of pcDNA-spike with BamHI and EcoRV, the resulting 5'-end of the gene was ligated with the PCR product into the pCG1 vector and designated SARSS-pCG1 (Fig. 1). Immunofluorescence analysis was performed as described previously.6 For the detection of the SARS-CoV S protein, a rabbit antiserum directed against SARS-CoV was used (kindly provided by Dr. Eickmann).

Discussion And Outlook

We were able to show that the SARS-CoV receptor ACE2 is used by the recently identified hCoV-NL63 for entry into target cells. Simultaneously, the same observation was reported by Smith and colleagues (M.K. Smith, et al., chapter 4.13). The interaction of NL63-S with ACE2 was unexpected, as NL63-S and SARS-CoV-S share no significant amino acid homology. In contrast, NL63-S is highly related to the glycoprotein of hCoV-229E, which binds hAPN CD13, and the hAPN CD13 interaction domain is well conserved in NL63-S. The most striking difference between the S-proteins of hCoV-NL63 and -229E is a 178 amino acid extension that is exclusively present in NL63-S. This unique domain, however, is dispensable for ACE2-interaction thus, amino acids in the highly conserved central portions and C-termini within the S-proteins of hCoV-229E and hCoV-NL63 determine the recognition of their respective receptors. Therefore, detailed point mutagenesis in combination with the determination of the...

Weaknesses Facilitating Emergence And Re Emergence

The weakening of the public health infrastructure for infectious disease control is evidenced by failures such as in mosquito control in Latin America and Asia with the re-emergence of dengue now causing major epidemics in the vaccination programs in eastern Europe during the 1990s, which contributed to the re-emergence of epidemic diphtheria and polio and in yellow fever vaccination, facilitating yellow fever outbreaks in Latin America and sub-Saharan Africa, including a large urban outbreak that occurred in Cote d'lvoire in 2001. It is also clearly demonstrated by the high levels of hepatitis B and the nosocomial transmission of other pathogens such as HIV in the former USSR and Romania, and the nosocomial amplification of outbreaks of Ebola in Zaire, where syringes and failed barrier nursing drove outbreaks into major epidemics.

Immediate hypersensitivity

Nations have imposed testing requirements as conditions of entry, denying entry to those who test positive for the virus. Whereas the WHo stresses the importance of cooperation in fighting the pandemic, these countries, including the United States, continue to exclude immigrants and aliens who are infected with HIV. Many countries, however, have heeded the WHO. Some have altered their restrictive travel and immigration laws to allow the entry of HIV-positive aliens. Several countries require HIV testing, not as a condition for exclusion, but as an alert to domestic health care facilities or other care givers within the country. Still others explicitly admit HIV-positive aliens within their borders, following WHo's spirit of global solidarity.

Bacterial Agents Of Noninflammatory Diarrhea

Vibrio cholerae belongs to the family Vibrionaceae and has been the cause of seven cholera pandemics since 1817. It is transmitted by contaminated food and water. Food-borne transmission often occurs by ingestion of raw or undercooked shellfish. Since the acid-sensitive bacteria must pass through the stomach to colonize the small intestine, a high inoculum of 109 organisms is required to cause disease. The diarrhea can be extremely severe, with characteristic rice water stools, which can lead to rapid dehydration, circulatory collapse, and death. accumulation of cAMP in enterocytes, and increase in secretion of chloride and water. Increased release of water into the intestinal lumen leads to secretory diarrhea. CT is encoded by the ctxAB genes carried on a filamentous bacteriophage. The receptor for the phage is a type IV fimbria, called the toxin-coregulated pilus (TCP), which is an essential colonization factor of V. cholerae. The gene encoding TCP is located on a 40-kb...

Mqmayrfngigvtqnvlyenqkqianqfnkaisqiqesltttstalgklqdvvnqnaqalntlvkqlssnfgaissvln

We investigated the orientation of the helicies in the HRN10 HRC complex by introducing disulfide bridges. Engineering a gly-gly-cys sequence onto the N- or C-termini of HRC and the N-termini of the HRN10 peptide allowed us to covalently link the peptides together, locking them into either a highly stable soluble form (the correct orientation) or a less stable form composed of head-to-tail aggregates (the incorrect orientation). Temperature denaturation studies showed that the antiparallel orientation was favored by an increase in stability (by 19oC) and solubility ( 5 mg mL). Surprisingly, the CD spectra of the covalently linked antiparallel complex (-19200o*cm2*dmol-1 at 222 nm rather than -34,500o*cm2*dmol-1) showed that it either contained unfolded residues at one end, or one of the peptides exists in a partially helical form. The crystal structure of the 6HB of SARS S was recently published, and confirmed that the 6HB is not 100 helical and contains...

Copynumber polymorphisms CNPs A form of

Coronaviridae Family of single-stranded RNA viruses responsible for respiratory diseases. The outer envelope of the virus has club-shaped projections that radiate outwards and give a characteristic corona appearance to negatively stained virions. A coronavirus is responsible for SARS.

Disease Detectives Today

They watch for the emergence of a new disease or an old microbial adversary using a network of doctors and high-tech equipment like satellites and the Internet. The WHO is continuously monitoring the World Wide Web with a customized search engine called the Global Public Health Intelligence Network, listening for rumors and reports of suspicious disease-related events. Online eavesdropping led to the early detection of the 2003 outbreak of SARS (severe acute respiratory syndrome). Epidemiologists from the World Health Organization conduct research on the Ebola virus. Epidemiologists study the incidence, spread, and control of infectious diseases.

Major histocompatibility complex MHC A

Similarities and differences between malaria and HIV bear noting. Like HIV, malaria kills millions of people each year and is a scourge of developing nations in Africa, India, Southeast Asia, and South America. Most people who contract malaria or HIV are poor. Whereas HIV is pandemic, spread from person to person by sexual contact in an increasingly mobile world, malaria is endemic, dependent on a local symbiosis between infected

Model complexity and data

Epidemiological models of specific systems are most successful when calibrated by high-quality data and a good quantitative understanding of the natural history of infection. This was the case for both foot and mouth disease and childhood infections such as measles in England and Wales. Specifically, these systems provided both an estimate of patterns of host susceptibility at epide-miologically meaningful spatio-temporal scales (farms for foot and mouth disease cities for measles) and disease-incidence data. Together, these elements allow a key calibration how the (imperfectly known) host-contact network determines the pattern of transmission. In contrast, recent models of smallpox and pandemic influenza (Halloran et al., 2002 Ferguson et al., 2005) while often well constructed using cutting-edge modelling techniques are necessarily hampered by a lack of epidemiological data and therefore an incomplete quantitative understanding of the precise transmission network. The public health...

Ace2 Expression In Airliquid Interface Cultured Airway Epithelia Is Polarized

To understand the potential role for ACE2 as the SARS-CoV receptor in the respiratory tract, we first looked for evidence of ACE2 protein expression in human lung tissue by Western blot. ACE2 was identified in lysates from human conducting airway and distal lung tissues, but this result did not indicate which cell types expressed ACE2 (data not shown). We next evaluated ACE2 protein expression in well-differentiated primary cultures of airway epithelia by immunohistochemistry. The signal for ACE2 was more abundant on the apical rather than the basolateral surface (Figure 1A). Furthermore, the signal intensity was strongest on ciliated cells, as demonstrated by co-localization with beta-tubulin IV, a marker of cilia,11 suggesting that ciliated cells express ACE2 abundantly. To confirm a polar distribution of ACE2 in differentiated epithelia, selective apical or basolateral surface biotinylation with subsequent immunoprecipitation was performed (Figure 1B). Western blot analysis of...

Polarization Of S Protein Pseudotyped Fiv Viral Entry

To evaluate the polarity of entry of the SARS-CoV in airway epithelia, we prepared feline immunodeficiency virus (FIV) virions pseudotyped with SARS S protein, and this vector was used to contrast the efficiency of entry in A549 cells, poorly differentiated (submerged) human airway epithelia, and well-differentiated epithelia. Only well-differentiated epithelial cells showed significant P-galactosidase expression following transduction (Figure 2D). The ACE2 dependence of transduction with SARS S protein FIV pseudotyped virions, which also express P-galactosidase, was first evaluated on 293 cells with or without co-transfection with human ACE2 cDNA. The result indicated that 293 cell transduction with this vector was almost completely ACE2-dependent. To further evaluate the ACE2 dependence of human airway epithelia for SARS-CoV, we transduced poorly differentiated A549 cells and submerged primary airway epithelia that do not express constitutive ACE2 with increasing MOIs of an...

Discussion And Conclusions

As cells expressing human or mouse ACE2 revealed that feACE2 functions as a SARS-CoV receptor as efficiently as human ACE2, while mouse ACE2 does less the SARS-CoV S protein.10 From these observations, it is postulated that animal species whose ACE2 functions as an efficient SARS-CoV receptor would be a susceptible host species for this virus. To establish a good animal model for SARS, a ferret model would be a good candidate. Furthermore, transgenic mouse expressing ferret or human ACE2 may serve a useful animal model for SARS-CoV infection.

Identification Of Nonneutralizing Epitopes In S Protein

The S protein of SARS-CoV induces antibody responses in infected patients and in mice and rabbits immunized with the inactivated SARS-CoV.11,12 To define its immuno-epitopes, a set of 168 peptides spanning the entire sequence of the S protein of SARS-CoV strain TOR2 (each peptide contains 17 amino acid residues with 9 residues overlapping with the adjacent peptides) were synthesized and used in the Pepscan analyses against the convalescent sera from SARS patients. It revealed that the S protein contained five linear immunodominant sites corresponding to the sequences of residues 9-71, 171-224, 271-318, 528-635, and 842-913 (designated as sites I to V). The immunodominant site I-III, and V reacted with more than 50 of the convalescent sera from SARS patients, and the site IV was reactive with more than 80 of SARS sera. All of 168 overlapping peptides were also used as probes to localize the immunodominant epitopes of S protein in the SARS-CoV-immunized mice and rabbits. Interestingly,...

Identification Of S Protein Rbd As A Major Target Of Neutralizing Antibodies

We found that convalescent sera from SARS patients contained high titers of RBD-specific antibodies.14 To identify neutralizing epitopes of SARS-CoV S protein, a fusion protein containing the RBD (residues 318-510) linked to human IgG1 Fc fragment (designated RBD-Fc) was used to isolate RBD-specific antibodies by immunoaffinity chromatography from patient antisera.14 The efficiencies of depletion and recovery of the RBD-specific antibodies were monitored by measuring the reactivity of the starting sera, the corresponding flowthroughs and eluted antibody fractions by ELISA against the RBD and S1 subunit. Neutralizing activities of the samples of the starting sera, flowthroughs and eluates were determined using SARS pseudovirus system. Strikingly, the neutralizing activity of immune sera was dramatically reduced after depletion of anti-RBD antibodies, while anti-RBD antibodies in the eluates possessed higher potency than the antibodies in the flowthroughs to neutralize SARS pseudovirus,...

The Rbd Of S Protein Contains Multiple Conformational Epitopes That Induce Potent Neutralizing Antibodies

To evaluate whether the RBD can serve as an effective vaccine, the RBD-Fc protein was used as an immunogen to immunize mice and rabbits.10, 13 All animals (mice and rabbits) developed robust antibody responses against RBD-Fc after boosting. The antisera contained high titers of antibodies specific for the RBD as shown by ELISA using S1 subunit as an antigen. The mean endpoint titers of mouse and rabbit antisera to the S1 protein were 1 625,000 and 1 312,500, respectively. The antisera were further tested for their neutralizing activity using two different assay systems, i.e., infection of SARS-CoV in Vero E6 and of SARS pseudovirus in 293T cells expressing ACE2. Strikingly, both mouse and rabbit antisera were able to effectively neutralize live SARS-CoV infection with mean 50 neutralization titers of 1 15,360. Infection of ACE2-expressing 293T cells by SARS pseudovirus could be potently inhibited. To characterize the neutralization determinants on the RBD of S protein, we isolated a...

Sexually transmitted diseases

Researchers at Chinese University in Hong Kong have released preliminary findings that suggest SARS is much milder in children and teens than in adults. Scientists found that while teens had symptoms similar to those of adults (muscle aches and chills) younger children tended to have milder symptoms, such as coughs and runny noses, and recovered sooner. The first case of SARS was diagnosed in November 2002 in southern China's Guangdong province, and within one month the province reported 300 cases. The disease quickly spread to 20 other countries, including parts of Asia, Europe, and North America by April 2003 there were 3,000 cases of SARS reported and more than 100 deaths worldwide. To put things in perspective, however, flu-related complications kill more than 36,000 people every year in the United States alone. The SARS epidemic had faded away by the end of summer 2003. A few new cases appeared in 2004. SARS is caused by a previously unrecognized coro-navirus these viruses are a...

Filaments See thick filaments thin filaments intermediate filaments and microfilaments

Filoviridae Family of single-stranded RNA viruses, similar in some respect to rhabdoviruses. Marburg and Ebola viruses are the only two members of the family at present. Filovirus infections seem to cause intrinsic activation of the clotting cascade, leading to haemorrhagic complications and high mortality. Morphologically, virions are very long filaments (up to 14 i,m, 70 nm thick), sometimes branched. The RNA is contained within a nucleocapsid that is surrounded by a cell-derived envelope.

Overall Structure Of Coronavirus Main Proteinase

The functional importance of the SARS-CoV M 0 in the viral life cycle makes it a preferred target for discovering anti- SARS drugs.4-7 However, in order to apply rational drug design or virtual screening, information on the structure of the target enzyme is required. Initially, this came from homology models of the SARS-CoV M ro that were constructed on the basis of crystal structures of human CoV (HCoV) 229E Mpro and of porcine transmissible gastroenteritis virus (TGEV) Mpro that we had previously determined.4,8 The SARS virus enzyme shares about 40 sequence identity with these proteinases of group I coronaviruses. More recently, the crystal structure of the SARS-CoV M ro has been determined.9-11 As with other CoV M ros, the molecule comprises three domains (Figure 1). Domains I (residues 8-101) and II (residues 102-184) are Figure 1. The three domains of the SARS-CoV Mpro monomer. The catalytic dyad (His41 Cys145, shown in black) is located in the interface between domains I and II....

Molecular Dynamics Simulations

We have confirmed by molecular dynamics (MD) simulations that large conformational changes of the observed type can indeed be triggered by protonation of His163 and deprotonation of His172.10 In three different 10-ns simulations at pH 6.0, 7.6, and 8.0, we found the same type of rearrangements as seen in the crystals. This is reassuring, because it should not be forgotten that unless the crystals diffract to better than 1.0 A resolution, X-ray diffraction cannot normally determine hydrogen positions because of their low scattering power. The force fields used in MD simulations, on the other hand, fully take into account the hydrogens bound to non-carbon atoms. Thus, because these simulations yield the same conformational rearrangements as those seen by X-ray diffraction, the interpretation of the crystallographic results is likely to be correct. Also, our preliminary NMR data with 15N-labeled SARS-CoV Mpro (J. George et al, unpublished) appear to support these conclusions. In addition...

Can Hiv Destroy Your Speech

Jonas Salk, the famous polio researcher, was the first to suggest vaccination of HIV-infected people with HIV vaccine products. Today most clinicians, researchers, and scientists would agree that a preventive HIV vaccine is the world's best hope of ending the AIDS pandemic. Many scientists currently believe that finding a safe and effective vaccine is possible. The need for an HIV vaccine is most acute in developing countries, where 90 percent of all new HIV infections are occurring. And the epidemic is expanding rapidly in many of those coun

Microbiological Terrorism

Although this nightmarish disaster might seem like science fiction, it is paralleled closely by historical fact. The real ancestral microbe was Yersinia pseudotuberculosis. The genetic changes it underwent occurred in nature, probably in the past 1500 to 20,000 years. During that time, the bacterium evolved, as described, into a far more deadly form that was given the name Y. pestis, the bacterial agent of plague, or black death. Several times during the Middle Ages, and as recently as the twentieth century, the plague reached pandemic scales, wiping out huge segments of humanity.

Envelope Switching Flexibility of Rhabdovirus Envelopes

Ebola virus G2B'3 Ebola virus G2A'3 gous surface glycoprotein was not only incorporated into the virions but was active in receptor binding and subsequent membrane fusion. HIV-1 gp160 surrogate VSV and RV able to amplify only on cells expressing the HIV-1 receptor confirmed the potential of rhabdoviruses in retargeting (Johnson et al. 1997 Foleyet al. 2002). An increasing number ofVSV and RV pseudotype and surrogate viruses carrying glycoproteins from a variety of viruses, including, for example, Ebola virus or hepatitis C virus (HCV), have been used in the following for purposes of retargeting and for presentation of antigen on the surface of virus particles (Table 2).

Virucidal Effect Of A Newly Developed Nickel Alloy On Mouse Coronavirus

A newly recognized disease, severe acute respiratory syndrome (SARS), was first reported in China in February 2003. A few months after the first outbreak of SARS, the disease was transmitted worldwide in more than 20 countries of Asia, Europe, and North America. A novel coronavirus (CoV) was detected in patients with SARS and identified as causative agent. Civet cats have been suspected as natural host of SARS CoV, which infects human beings by oral or intranasal route the infected hosts sheds the virus into air through respiratory route and or feces from intestinal tract. The routes of entry and shedding of SARS CoV is similar to those of mouse hepatitis virus (MHV mouse CoV), which causes a variety of diseases such as diarrhea, hepatitis, encephalitis, and wasting syndrome of nude mice. To control SARS CoV infection, several disinfectants and tools were examined. Recently, He et al.1 reported an inactivation of SARS CoV by silver alloy. Sagripanti et al2 reported virucidal effect of...

Plasticity Of The Substratebinding Site

A special feature first discovered for the SARS-CoV M ro (but most probably present in all coronavirus main proteinases) is that in the monoclinic crystals grown at pH 6.0, the two monomers have different conformations around the S1 substrate-binding site, because the loop 138-145, in particular Phe140, as well as Glu166 undergo dramatic conformational rearrangements. As a result, one protomer exists in an active and the other in an inactive conformation.9 In the latter, the S1 substrate-binding pocket has virtually collapsed as a consequence of the reorientation of Glu166, and the oxyanion hole no longer exists due to the conformational change of residues 138-145. When the crystals are equilibrated at pH 7.6 and 8.0, both monomers are in an active conformation.9 We have proposed9,10 that these conformational changes are controlled by the protonation state of His163, an absolutely conserved residue at the bottom of the S1 substrate-specificity pocket (Figure 2). This subsite is...

Narrowly utilitarian considerations

There are, however, additional reasons for seeking a better understanding of the species richness and taxonomic details of neglected biota, especially invertebrates. For one thing, most of the benefits of modern medicine are oriented to the developed world (Kremer and Glennerster, 2004) the protozoan and helminth parasites which cause mortality and morbidity in developing countries deserve more taxonomic attention, both to themselves and to their vectors and (in some instances) non-human animal reservoirs. The transmutation of what was once traditional and local bushmeat consumption into a full-blown and indeed globalizing industry underlines this point in a different way (Bell et al., 2005). HIV-1, HIV-2, and SARS are three viruses which made it into human populations this way. How many are yet to come

Insights From Animal Ace2 And Animalderived Viral Isolates

The ability of the ACE2 proteins of mice, rats, and palm civets to support SARS-CoV infection has been compared with that of human ACE2.22, 51 Compared with cells expressing human receptor, SARS-CoV infection was less efficient in cells expressing murine ACE2. Infection was nearly absent in those expressing rat ACE2. Consistent with a role for palm civets in transmitting virus, palm civet ACE2 supported SARS-CoV infection as efficiently as human ACE2. These results correlated with affinity of each of these receptors for the S protein and its RBD.22, 51 Chimeras between human and rat ACE2 receptors were used to identify the S-protein binding site on ACE2.22 Mutation of four rat ACE2 residues (82-84 and 353) to their human equivalents converted rat ACE2 into an efficient SARS-CoV receptor. Residues 82-84 comprise a glycosylation site on the rat receptor that is not present on mouse, palm civet, or human receptor. Residue 353 is a histidine in mouse and rat receptors, and a lysine in...

Polymerase And Helicase Activities

The coronavirus RdRp has been classified as an outgroup of the RdRp superfamily 1.36 It resides in the ORF1b-encoded nonstructural proteins 12, as was predicted about 15 years ago6 and now demonstrated for a bacterially expressed form of the SARS-CoV nsp12.37 The RdRp catalytic domain occupies the C-terminal two-thirds of nsp12,6 but also the N-terminal part of nsp12 seems to contribute to activity.37 Based on MHV co-immunoprecipitation data, the N-terminal part of nsp12 has been suggested to interact with other replicase subunits, specifically with nsp5 (3CLpro), nsp8, and nsp9,38 which is in line with the recently published crystal structure of an nsp7-nsp8 complex from SARS-CoV.39 The X-ray crystallography study by Zhai et al.39 provides first insights into the sophisticated architecture of the coronavirus replicase. It shows that eight molecules of each nsp7 and nsp8 assemble into a hexadecameric supercomplex that forms a hollow, cylinder-like structure, which, because of its...

Rnaprocessing Enzymes

A detailed sequence analysis by Gorbalenya, Snijder and colleagues of the SARS-CoV genome revealed that the enzymology of coronavirus RNA synthesis may be significantly more complex than previously thought.8 In this seminal study published in included (i) a 3'-to-5' exonuclease (ExoN) associated with nsp14, (ii) an endoribonuclease (NendoU) associated with nsp15, (iii) an S-adenosyl methionine-dependent ribose 2'-O-methyltransferase (MT) associated with nsp16, (iv) an ADP-ribose 1 -phosphatase (Appr-1 -pase) associated with the so-called X domain of nsp3, and (v) a cyclic phosphodiesterase (CPDase), which is only conserved in group II coronaviruses (excluding SARS-CoV). Four of the activities were found to be conserved in all coronaviruses, suggesting that they have an essential role in the coronaviral life cycle. Recently, the predicted exo- and endoribonuclease activities were established and characterized using bacterially expressed forms of the ExoN from SARS-CoV (Minskaia,...

Structure Of The Virion

The supramolecular architecture of SARS-CoV, FIPV, and MHV appears quite similar. Each virus is covered with spikes that extend 200 A from the peak density of the headgroups in the outer leaflet of the viral membrane. There appears to be a gap between adjacent end-projected spikes near the virion center (Fig. 2A right, for example). The arrangement of spike densities near the center of some particles approximates a rhombus, which would not be inconsistent with a paracrystalline organization of spikes as observed in the virions of pleomorphic arenavirus particles,17 or a local hexagonal close-packing of structural proteins as observed in retroviral particles.11 Coronavirus particles, as previously reported, appear pleomorphic, and deviate more sharply from a circular profile than other Figure 3. Ribonucleoprotein released from a spontaneously disrupted SARS-CoV particle. The viral ribonucleoprotein is shown at two levels of focus, (A, 4.5 jim below true focus B, 2.0 jim below true...

Newly Identified Coronaviruses In Human And Animals

After the SARS outbreak in 2003, two independent groups identified a novel CoV (HCoV-NL63) in humans.31,32 Similar to other classical human CoVs, this group 1 virus is associated with respiratory illnesses. Recent studies also indicated that this virus is a common respiratory pathogen in human populations.33,34 On the other hand, using conserved primers for CoVs, another novel human CoV virus (HCoV-HKUl) was recently identified.35 So far, this virus was reported to be found in a small number of patients with pneumonia in Hong Kong. Further epidemiological studies are required to demonstrate the clinical importance of this novel group 1 pathogen in global human populations.

Environment and Neurodegenerative Diseases

Parkinson's disease is also linked with the great influenza epidemic of 1917. A subgroup of people who survived the epidemic subsequently came down with severe Parkinson's disease. Here the precipitating cause might have been a virus. These patients were some of the first to be treated with L-dopa by the famed neurologist-author Oliver Sacks. Sacks subsequently wrote a book on this experience, called Awakenings, that was turned into a well-received film.

Results

A series of three stem-loops denoted I, II, and III had been predicted in the BCoV 5' UTR. These predictions were supported in part by nuclease mapping experiments and by DI replication assays.3,7 However, it was puzzling to us that the predicted stem-loops I and II of BCoV are not conserved amongst group 2 coronaviruses. Here we used Vienna RNA 1.5 4 to predict the 5' UTR secondary structures of nine coronaviruses (summarized in Table 1). The results of Vienna RNA folding predictions carried out for MHV and SARS-CoV are shown in Figure 1. All coronavirus 5' UTR secondary structural models are strikingly similar, and are characterized by three major helical stems, denoted SL1, SL2, and SL4. Some sequences show a fourth stem-loop, denoted SL3, in which the leader TRS (TRS-L) is folded into a hairpin loop. SL2 is absolutely conserved and previously unrecognized. The (C U)UUG(U C) pentaloop sequence is the most highly conserved contiguous run of nucleotides in the entire 5' UTR outside...

D1826a

Sulea and co-workers noted structural signatures for strict specificity (Sulea et al., 2005) present in HAUSP and also in some of the coronavirus papain-like proteases, which form part of the substrate-binding site. In the case of SARS-CoV PLpro the residues Y1804 and Y1813 occlude the substrate-binding site, imposing the requirement for the small diglycine residues at the cleavage site (Sulea et al., 2005). Our alignment of the amino acid sequences of 16 papain-like proteases from nine coronaviruses shows that the signature sequence is present in twelve of these sequences. This suggests that these proteases may also have deubiquitinating activity, though this remains to be experimentally verified.

Lgvkgsg H

Multiple sequence alignment of DUB signature sequences from coronavirus papain-like proteases. The papain-like protease domain amino acid sequences (two domains termed as P1 and P2 one domain termed as PLpro) of nine coronaviruses were aligned using the ALIGN program (SciEd). The residues proposed to be part of the substrate binding site for deubiquitination are boxed. Identical residues are highlighted in light gray. The catalytic histidine residue is boxed in thick black or highlighted in gray. Papain-like proteases which are predicted to lack deubiquitinating activity are indicated by a thick vertical line. Abbreviationas are as follows SARS CoV- Severe acute respiratory syndrome coronavirus, Urbani strain (AY278741) MHVJ- Mouse hepatitis virus, strain JHM (NC_001846) BCoV- bovine coronavirus (NC_003045) HCoV-OC43-Human coronavirus OC43 (AY585228) HCoV-229E- Human coronavirus 229E (X69721) HCoV-NL63- Human coronavirus NL63 (NC_005831) TGEV- Transmissible gastroenteritis...

Swine Influenza

Swine Influenza

SWINE INFLUENZA frightening you? CONCERNED about the health implications? Coughs and Sneezes Spread Diseases! Stop The Swine Flu from Spreading. Follow the advice to keep your family and friends safe from this virus and not become another victim. These simple cost free guidelines will help you to protect yourself from the swine flu.

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