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Type Species |
(SV-40) |
Virions are non-enveloped 40 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 25 
106. Buoyant density of virions in sucrose and CsCl gradients is 1.20 and 1.34-1.35 g/cm3, respectively. Virion S20w is 240S. Virions are resistant to ether, acid and heat treatment (50°C, 1 hour). Virions are unstable at 50°C for 1 hour in the presence of 1M MgCl2.
Virions contain a single molecule of circular dsDNA. The genomic size is fairly uniform: it is about 5 kbp (e.g., Simian virus 40 (SV-40) [strain 776] has 5,243 bp, JC polyomavirus (JCPyV) [Mad1] has 5,130 bp, BK polyomavirus (BKPyV) [Dun] has 5,153 bp, Murine polyomavirus (MPyV) [A2] has 5,297 bp, Baboon polyomavirus 2 (BPyV) has 4,697 bp). The DNA constitutes about 10-13% of the virion by weight. The G+C content varies between 40-50%. 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 proteins with Mr ranging from 3-88 103 (Table 1). Three structural proteins, VP1, VP2 and VP3 make up the polyomavirus capsid; of these, VP1 is the major component. A fourth protein, agnoprotein, or LP1, may be produced and may facilitate the assembly of the polyomavirus capsid. It is not a structural component of the mature virion.
None present.
None present.
Genome Organization and Replication
Virions that attach to cellular receptors are engulfed by the cell and are transported to the nucleus. During a productive infection, transcription of the viral genome is divided into an early and late stage. Transcription of the early and late coding regions is controlled by separate promoters and occurs on opposite DNA strands (Fig. 2).
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 viral DNA replication. Their expression leads to derepression of some host cell enzymes and stimulation of cell DNA synthesis. Prior to the start of the late events, viral DNA replication is initiated in the nucleus. Translation of most 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, fatty acid acylation, ADP-ribosylation, methylamination, adenylation, glycosylation and sulphation. 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 infected cells.
Two to three non-structural proteins are expressed which include large T, middle (m)T and small t for mouse and hamster polyomaviruses, and large T and small t for the other species (e.g., SV-40, JCPyV, and BKPyV, Table 1). An exception is BPyV for which no mRNA encoding a protein of size comparable to the small t proteins of other viruses has been identified. An ORF for a third protein, ELP (Early Leader Protein) has been identified in the SV-40 genome; ORFs with the potential to encode a similar protein are present within the JCPyV and BKPyV genomes (Table 1). The function(s) of this polypeptide is unknown whereas the T proteins, first named for their involvement in tumorigenicity and transformation, play key roles in the regulation of transcription and DNA replication. The best characterized of these, the SV-40 large T protein, exhibits multiple functions that can be mapped to discrete domains.
Replication of the viral genome is initiated by the specific binding of the T antigen at a unique origin of replication and its interaction with host DNA polymerase(s). Due to the limited amount of genetic information encoded by the viral genomes, the polyomaviruses rely heavily upon cell machinery to replicate their DNA. Replication proceeds bi-directionally via a “Cairns” structure and terminates about 180° from the origin of replication. Late in the replication cycle, rolling circle-type molecules have been identified. The viral proteins involved in initiation may also promote elongation through helicase and ATPase activities.
Antisera prepared against disrupted virions detect antigens shared with other species in the genus. Members of the genus Polyomavirus can be distinguished antigenically by neutralisation, hemagglutination inhibition and immunoelectron microscopy tests. Polyclonal and monoclonal antibodies can be used to demonstrate cross-reactivity between the T proteins of the primate polyomaviruses.
Each virus has a specific host range in nature and in cell culture. The host range is often highly restricted, although cells which fail to support viral replication may be transformed via the action of the early gene products.
Virus spread occurs by reactivation of persistent infections in the mother during pregnancy, by low level shedding of virus in urine, and rarely by tissue transplantation (in humans). Transmission may also involve contact and airborne infection. Vectors appear not to play a role in transmission. The polyomaviruses are distributed worldwide, and persistent infections are frequently established, usually early in life. The polyomaviruses often demonstrate highly tissue-specific expression. Involvement of the kidney is frequently observed and viruria may be noted, especially in immunodeficient hosts. Infection in humans has been associated with some pathologic changes in the urinary tract. One of the human polyomaviruses, JCPyV, may infect and destroy oligodendrocytes of the central nervous system, thereby leading to a fatal demyelinating disease termed progressive multifocal leucencephalopathy (PML). SV-40 may cause a PML-like disease in rhesus monkeys. Most polyomaviruses have oncogenic potential in rodents. JCPyV can induce brain tumors in owl monkeys. Under some conditions mouse polyomavirus produces a wide variety of tumors in its natural host. Transformation and oncogenicity result from an expression of virus-specific early proteins and their interaction with products of specific cellular genes (p53, pRB and others). In transformed and tumor cells the polyomavirus genomes are usually integrated into the host cell DNA.
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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African green monkey polyomavirus |
[K02562] |
(AGMPyV) |
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B-lymphotropic polyomavirus |
(LPyV) | |
|
Baboon polyomavirus 2 |
(PPyV) | |
|
BK polyomavirus |
(BKPyV) | |
|
Bovine polyomavirus |
[D00755] |
(BPyV) |
|
Stump-tailed macaque virus |
||
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Fetal rhesus kidney virus |
||
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Budgerigar fledgling disease polyomavirus |
(BFPyV) | |
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Hamster polyomavirus |
[X02449] |
(HaPyV) |
|
JC polyomavirus |
[J02226] |
(JCPyV) |
|
Murine pneumotropic virus |
[M55904] |
(MPtV) |
|
Kilham polyomavirus |
(KPyV) | |
|
Murine polyomavirus |
[J02288] |
(MPyV) |
|
Rabbit kidney vacuolating virus |
(RKV) | |
|
Simian virus 12 |
(SV-12) | |
|
Simian virus 40 |
[J02400] |
(SV-40) |
Tentative Species in the Genus
None reported.
Unassigned Members in the Family
None reported.
Phylogenetic Relationships within the Family
Not available.
Until this report, the genus Polyomavirus was assigned as one of two genera within the family Papovaviridae (the other genus being Papillomavirus).
Polyoma: from Greek poly, “many”, and -oma, denoting “tumors”.
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