Pentamer Pentamer Contacts

The T 1 particle structure reveals the pentamer-pentamer bonding in this assembly (Chen et al., 2000). Because all 12 pentamers are pentavalent, all contacts between L1 monomers are identical. This bonding is accomplished by helix-helix interactions between the C-terminal lateral projections (Fig. 5.4 and Fig. 5.5). Helix 4 from each pentamer projects outward to interact with helices 2 and 3 of a neighbor, using strong hydrophobic interactions. The remainder of the C-terminal chain after...

The E1 DBD

C-terminal to the N-terminal domain is a well-conserved region (aa 150-300), which corresponds to the very well characterized E1 DNA-binding domain (DBD). This domain provides sequence-specific binding of E1 to the E1 BS present in the ori. The structures of the E1 DBD from BPV-1 and HPV-18 have been solved by X-ray crystallography (Auster and Joshua-Tor, 2004 Enemark et al., 2000, 2002). Remarkably, the structure of the BPV E1 DBD is very similar to the NMR structure of the DBD from SV40 T-ag...

Structure Determination

Electron microscopy and image analysis of negatively stained SV40, polyoma, and papillomaviruses (Klug, 1965 Anderer et al., 1967 Finch and Klug, 1965) established that the virion capsids were comprised of subunits (capsomeres) arranged in an icosahedral lattice (Fig. 5.1). The T, or triangulation, number nomenclature was derived by Caspar and Klug to explain the possible icosa-hedral symmetries of capsids of various sizes (Caspar and Klug, 1962). Strict icosahedral symmetry implies 60 x T...

Pathogenicity Versus Latency

Infections with PVs are clearly the cause of common and genital warts and a central causal factor in the etiology of cervical cancer. While this concept is well confirmed, it is nevertheless erroneous to characterize PVs as aggressive neoplastic agents. Among the arguments for this statement is the observation of a huge number of HPV types in the skin of asymptomatic individuals (Antonsson et al., 2000, 2003 Antonsson and Hansson, 2002) and the wide variety of HPV types in healthy individuals...

The 1930s and 1940s Biology of the Shope Papillomavirus and Other Animal Papillomaviruses

Papillomaviruses were the second class of viruses, after retroviruses, shown to induce malignant tumors (Shope, 1933). As such, the Shope papillomavirus, which is now designated the cottontail rabbit papillomavirus (CRPV), became an important experimental model of viral tumorigenesis. Not only did infectious extracts induce benign papillomas in cottontail and domestic rabbits, but some of the benign lesions progressed to squamous cell cancers, the first demonstration that a mammalian virus...

Papillomavirus Species

Traditionally, novel genomic PV isolates have been described as types. As will be discussed below, today a PV type is defined as a complete PV genome whose L1 gene nucleotide sequence differs by at least 10 percent from that of any previously described PV type. According to this definition the genomes of PV types are as remotely related to one another as those of many distinct host species, for example, humans and the four living ape species. In addition, PV Table 3.2. The Most Frequently...

Methods to Study the HPV Life Cycle

Hpv Pictures Life Cycle

Study of the papillomavirus life cycle has been hampered by the inability of these viruses to replicate to high titer in the laboratory. Initial studies on the life cycle involved descriptive studies of the distribution of viral genomes and gene products in naturally occurring lesions in animals and humans. Cells transformed in culture by bovine papillomavirus were regarded as a model of the early phase of infection, while the outer epithelial layers of productively infected warts represented...

The Viral Origin of DNA Replication

The cis-acting sequences required for papillomavirus DNA replication have been defined for a number of papillomaviruses using transient replication assays with E1 and E2 expressed from heterologous promoters (Chiang et al., 1992b Del Vecchio et al., 1992 Lu et al., 1993 Remm et al., 1992 Sverdrup and Khan, 1995 Ustav et al., 1991). In all cases, a short sequence (60-80 bp) located between the URR LCR and the early open reading frames (ORFs), has been identified as a minimal origin of...

Human Papillomavirus E6 Proteins 10221 HPV E6 and p53

Most studies on thehuman papillomavirus E6 proteins have focused on thehigh-risk HPV types associated with human cervical cancer. The first activity identified for the high-risk HPV E6 proteins was the ability to form a complex with p53 (Werness et al., 1990), a property not shared with the low-risk HPV E6 proteins. Through this interaction, high-risk E6 can block the ability of p53 to transcriptionally activate p53-responsive promoters (Mietz et al., 1992). The steady state levels of p53 are...

The 1970s to the Early 1990s Viral Genetics and the Emergence of HPV as a Medically Important Virus

Molecular cloning and related techniques developed in the mid-1970s partially overcame the experimental limitations to studying papillomaviruses, leading to renewed interest in these viruses and to a wealth of new information about them. During the late 1970s and early 1980s, papillomavirus research followed two main themes experimentally oriented studies of animal papillomaviruses, especially BPV1, and more clinically oriented studies of HPVs. By the second half of the 1980s, clinical and...

Principles of Human Tumor Virology

1 Microbiology and Tumor Biology Center (MTC), Karolinska Institutet, S-171 77 Stockholm, Sweden 2 Departments of Genetics and Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8005 Viruses containing either RNA or DNA genomes can cause tumors, and studies of tumor viruses have provided important insights into basic molecular and cellular processes. Retroviruses are the only class of RNA viruses that are known to cause tumors in animals, whereas several different...