106. Buoyant density of virions in sucrose and CsCl gradients is 1.20 and 1.34-1.35 g/cm3, respectively. Virion S20w is 300S. Virions are resistant to ether, acid and heat treatment (50°C, 1 hour).
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Type Species |
(CRPV) |
Virions are non-enveloped, 55 nm in diameter. The icosahedral capsid is composed of 72 capsomers in skewed (T = 7) arrangement (Fig. 1). Filamentous and tubular forms are observed as a result of aberrant maturation.
Physicochemical and Physical Properties
Virion Mr is 47 106. Buoyant density of virions in sucrose and CsCl gradients is 1.20 and 1.34-1.35 g/cm3, respectively. Virion S20w is 300S. Virions are resistant to ether, acid and heat treatment (50°C, 1 hour).
Virions contain a single molecule of circular dsDNA. The genomic size ranges between 6800 and 8400 bp. The DNA constitutes about 10-13% of the virion by weight. The G+C content is 40-60%. In the mature virion the viral DNA is associated with host cell histone proteins H2a, H2b, H3 and H4 in a chromatin-like complex.
The virus genomes encode 8-10 proteins with Mr ranging from 7-73 103 (Table 1). L1 and L2 make up the papillomavirus capsid. E1 and E2 are involved in papillomavirus replication and in intragenomic regulation (E2). E5, E6 and E7 induce cellular DNA replication. E4 may represent a late function and binds to specific cytoskeleton structures. Genetic evidence has not been presented that associates specific viral proteins with the E3 and E8 ORFs.
None present.
None present.
Genome Organization and Replication
Virions that attach to cellular receptors are engulfed by the cell and the DNA is uncoated and transported to the nucleus. During the productive infection, transcription of the viral genome is divided into an early and late stage. Transcription of the early and late coding regions occurs from the same strand in one direction only.
Precursor mRNAs undergo post-transcriptional processing that includes capping and polyadenylation of the 5
- and 3-termini, respectively, as well as splicing. Efficient use of coding information involves differential splicing of the messages and use of overlapping ORFs. Early mRNAs encode regulatory proteins that may exhibit trans-activating properties. These include proteins that are required for DNA replication. Their expression leads to depression of some host cell enzymes and may also stimulate host cell DNA synthesis. Prior to the start of the late events, viral DNA replication is initiated in the nucleus. Translation of the late transcripts produces structural proteins that are involved in capsid assembly. Post-translational modifications of some early and late viral proteins include phosphorylation, N-acetylation, ADP ribosylation and other events. Several of the viral proteins contain sequences, termed nuclear localization signals, which facilitate transport of the proteins to the host cell nucleus where virion maturation occurs. Virions are released by lysis of the virus-producing cells.
The genomes of most members of the family Papillomaviridae that have been sequenced contain 9-10 ORFs, labelled E1-E8 and L1-L2 (Fig. 2). Some members lack the E3 and E8 ORFs. Proteins encoded by the E ORFs, with the possible exception of E4, represent non-structural polypeptides involved in transcription, DNA replication and transformation, whereas those encoded by the L ORFs represent structural proteins. Replication of the viral genome is initiated bi-directionally by specific binding of the E1 and E2 proteins at a unique origin of replication.
Serologic analysis of antigenic properties of papillomaviruses is still in an early phase. The L1 protein reveals type-specific domains, the L2 protein contains group-specific epitopes. The availability of papillomavirus-like particles, resulting from the expression of L1 or L1 and L2 in baculovirus, vaccinia virus or yeast systems, permits presently a detailed analysis of antigenic characteristics.
Papillomaviruses are highly host-species and tissue-restricted. All known members of the Human papillomavirus (HPV) group require terminal differentiation for replication and virion production. Infection appears to occur mainly via microlesions of proliferating basal layer cells. Except for inefficient replication of HPVs in raft cultures of human keratinocytes or more efficiently in human skin or mucosal xenografts in immunocompromised rodents, HPV replication has not been achieved in tissue culture systems.
Virus spread occurs by virus release from the surface of warts and papillomatous lesions which frequently contain large quantities of viral particles within their superficial differentiated layers. Virus reactivation is particularly frequent under conditions of immunosuppression. The mode of viral DNA persistence and possible clearance of HPV infections by immunological interference are still poorly investigated.
Transmission of viral infections occurs by close contacts. Papillomavirus types are distributed worldwide. They cause benign tumors (warts, papillomas) in their natural host and occasionally in related species. Frequently the infection leads to microlesions, barely or not at all visible without optical aid. Papillomas are induced in the skin and in mucous membranes, often at specific sites of the body. Some papillomatous proliferations induced by specific types of papillomaviruses bear a high risk for malignant progression. Specific human cancers (e.g., cervical carcinoma, anal, vulval and penile cancers, specific squamous cell carcinomas of the skin) have been linked to certain types of HPV infection (e.g., HPV-16 and HPV-18, HPV-5 and HPV-8 and several others). The viral DNA is often, but not always, present in an integrated form, particularly in cervical cancers, whereas skin carcinomas appear to harbor the viral genome in an episomal state. Cancer-linked anogenital HPV types immortalize efficiently a wide variety of human cells in tissue culture. Immortalization results from functions of the E6 and E7 genes of these viruses which act cooperatively, although both genes are able to immortalize human cells independently at low efficiency. E6 binds and degrades the cellular p53 protein, whereas E7 interacts with the cellular pRB and some related proteins. Interaction of the viral oncoproteins with cellular cyclin-dependant kinase inhibitors (p16, p21, p27) also emerge as important events in immortalization.
List of Species Demarcation Criteria in the Genus
Until the species demarcation criteria are established the list of species in the genus is provisional.
Provisional List of Species in the Genus
Official virus species names are in italics. Tentative virus species names, alternative names ( ), strains or serotypes are not italicized. Virus names, genome sequence accession numbers [ ], and assigned abbreviations ( ) are:
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Bovine papillomavirus |
[J02044] |
(BPV) |
|
Canine oral papillomavirus |
[L22695] |
(COPV) |
|
Cottontail rabbit papillomavirus |
[K02708] |
(CRPV) |
|
Deer papillomavirus |
(DPV) | |
|
(Deer fibroma virus) |
[M11910] |
|
|
European elk papillomavirus |
[M15953] |
(EEPV) |
|
Human papillomavirus |
[V01116] |
(HPV) |
|
Ovine papillomavirus |
[U83594] |
(OPV) |
Tentative Species in the Genus
There are 4 genotypes of BPV (BPV-1 to 4), 82 genotypes of HPV (HPV-1 to 82) and 2 genotypes of OPV (OPV-1 to 2) described in the literature. The taxonomic status of these viruses is uncertain. Other papillomaviruses from chaffinches, elephants and horses have also been described.
Unassigned Viruses in the Family
None reported.
Phylogenetic Relationships within the Family
Not available.
Until this report, the genus Papillomavirus was assigned as one of two genera within the family Papovaviridae (the other genus being Polyomavirus).
Papilloma: from Latin papilla, “nipple, pustule”, also Greek suffix -oma, used to form nouns denoting “tumors”.
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