Polyomaviridae

Source: Wikipedia, the free encyclopedia.
(Redirected from
Polyomavirus
)

Polyomaviridae
Micrograph showing a polyomavirus infected cell—large (blue) cell below-center-left. Urine cytology specimen.
Virus classification Edit this classification
(unranked): Virus
Realm: Monodnaviria
Kingdom: Shotokuvirae
Phylum: Cossaviricota
Class: Papovaviricetes
Order: Sepolyvirales
Family: Polyomaviridae
Genera

Polyomaviridae is a family of

Merkel cell cancer.[11]

Structure and genome

VP1, colored such that areas of the surface closer to the interior center appear blue and areas further away appear red. Rendered from PDB: 1SIE
​.

Polyomaviruses are

VP1, which is capable of self-assembly into a closed icosahedron;[13] each pentamer of VP1 is associated with one molecule of one of the other two capsid proteins, VP2 or VP3.[5]

WU virus, a human polyomavirus. The early region is shown on the left and contains the TAg (tumor antigen) proteins; the late region is on the right and contains the capsid proteins.[14]

The genome of a typical polyomavirus codes for between 5 and 9

cellular transformation; SV40 has an additional capsid protein VP4; some examples have an additional regulatory protein called agnoprotein expressed from the late region. The genome also contains a non-coding control or regulatory region containing the early and late regions' promoters, transcriptional start sites, and the origin of replication.[2][12][5][15]

Replication and life cycle

Murine polyomavirus VP1 in complex with the GT1a glycan. GT1a is shown in yellow and the VP1 monomer with a white surface and a blue protein backbone. A complex network of hydrogen bonds, many water-mediated, is shown at the binding surface by orange lines, with participating protein residues shown as sticks. Mutations of the two residues shown in cyan at the bottom of the figure can significantly affect pathogenicity. From PDB: 5CPW​.[16]

The polyomavirus life cycle begins with entry into a

Merkel cell virus with heparan sulfate.[15][17] However, in general virus-cell interactions are mediated by commonly occurring molecules on the cell surface, and therefore are likely not a major contributor to individual viruses' observed cell-type tropism.[15] After binding to molecules on the cell surface, the virion is endocytosed and enters the endoplasmic reticulum - a behavior unique among known non-enveloped viruses[18] - where the viral capsid structure is likely to be disrupted by action of host cell disulfide isomerase enzymes.[2][12][19]

The details of transit to the nucleus are not clear and may vary among individual polyomaviruses. It has been frequently reported that an intact, albeit distorted, virion particle is released from the endoplasmic reticulum into the cell cytoplasm, where the genome is released from the capsid, possibly due to the low calcium concentration in the cytoplasm.[18] Both expression of viral genes and replication of the viral genome occur in the nucleus using host cell machinery. The early genes - comprising at minimum the small tumor antigen (ST) and large tumor antigen (LT) - are expressed first, from a single alternatively spliced messenger RNA strand. These proteins serve to manipulate the host's cell cycle - dysregulating the transition from G1 phase to S phase, when the host cell's genome is replicated - because host cell DNA replication machinery is needed for viral genome replication.[2][12][15] The precise mechanism of this dysregulation depends on the virus; for example, SV40 LT can directly bind host cell p53, but murine polyomavirus LT does not.[20] LT induces DNA replication from the viral genome's non-coding control region (NCCR), after which expression of the early mRNA is reduced and expression of the late mRNA, which encodes the viral capsid proteins, begins.[19] As these interactions begin, the LTs belonging to several polyomaviruses, including Merkel cell polyomavirus, present oncogenic potential.[21] Several mechanisms have been described for regulating the transition from early to late gene expression, including the involvement of the LT protein in repressing the early promoter,[19] the expression of un-terminated late mRNAs with extensions complementary to early mRNA,[15] and the expression of regulatory microRNA.[15] Expression of the late genes results in accumulation of the viral capsid proteins in the host cell cytoplasm. Capsid components enter the nucleus in order to encapsidate new viral genomic DNA. New virions may be assembled in

VP4.[19] In some cases high levels of encapsidated virus result in cell lysis, releasing the virions.[15]

Viral proteins

Tumor antigens

The large tumor antigen plays a key role in regulating the viral life cycle by binding to the viral origin of DNA replication where it promotes DNA synthesis. Also as the polyomavirus relies on the host cell machinery to replicate the host cell needs to be in s-phase for this to begin. Due to this, large T-antigen also modulates cellular signaling pathways to stimulate progression of the cell cycle by binding to a number of cellular control proteins.[22] This is achieved by a two prong attack of inhibiting tumor suppressing genes p53 and members of the retinoblastoma (pRB) family,[23] and stimulating cell growth pathways by binding cellular DNA, ATPase-helicase, DNA polymerase α association, and binding of transcription preinitiation complex factors.[24] This abnormal stimulation of the cell cycle is a powerful force for oncogenic transformation.[citation needed]

The

E3 ligase regulating both cellular and viral oncoproteins.[28] Unlike for SV40, the MCV small T antigen directly transforms rodent cells in vitro.[29]

The

promoter. There it functions as an oncogene, while the tissue where the tumor develops is determined by the MMTV promoter.[citation needed
]

Capsid proteins

The polyomavirus capsid consists of one major component,

viral capsid, and in the interior of the capsid each pentamer is associated with one molecule of either VP2 or VP3.[5][30] Some polyomaviruses, such as Merkel cell polyomavirus, do not encode or express VP3.[31] The capsid proteins are expressed from the late region of the genome.[5]

Agnoprotein

The

JC virus, and SV40. It is essential for proliferation in the viruses that express it and is thought to be involved in regulating the viral life cycle, particularly replication and viral exit from the host cell, but the exact mechanisms are unclear.[32][33]

Taxonomy

The polyomaviruses are members of group I (dsDNA viruses). The classification of polyomaviruses has been the subject of several proposed revisions as new members of the group are discovered. Formerly, polyomaviruses and

Papovaviridae.[34] (The name Papovaviridae derived from three abbreviations: Pa for Papillomavirus, Po for Polyomavirus, and Va for "vacuolating.")[35] The polyomaviruses were divided into three major clades (that is, genetically-related groups): the SV40 clade, the avian clade, and the murine polyomavirus clade.[36] A subsequent proposed reclassification by the International Committee on Taxonomy of Viruses (ICTV) recommended dividing the family of Polyomaviridae into three genera:[37]

The current ICTV classification system recognises six genera and 117 species, of which five could not be assigned a genus. This system retains the distinction between avian and mammalian viruses, grouping the avian subset into the genus Gammapolyomavirus. The six genera are:[38]

The following species are unassigned to a genus:[38]

Description of additional viruses is ongoing. These include the sea otter polyomavirus 1[39] and Alpaca polyomavirus[40] Another virus is the giant panda polyomavirus 1.[41] Another virus has been described from sigmodontine rodents.[42] Another - tree shrew polyomavirus 1 - has been described in the tree shrew.[43]

Human polyomaviruses

Most polyomaviruses do not infect humans. Of the polyomaviruses cataloged as of 2017, a total of 14 were known with human hosts.

Trichodysplasia spinulosa-associated polyomavirus (TSV) is distantly related to MCV. Two viruses—HPyV6 and HPyV7—are most closely related to KI and WU viruses, while HPyV9 is most closely related to the African green monkey-derived lymphotropic polyomavirus (LPV).[citation needed
]

A fourteenth virus has been described.[44] Lyon IARC polyomavirus is related to raccoon polyomavirus.[citation needed]

List of human polyomaviruses

The following 14 polyomaviruses with human hosts had been identified and had their genomes sequenced as of 2017:[4]

Species Proposed genus Virus name Abbreviation NCBI RefSeq Year of discovery Clinical correlate (if any) References
Human polyomavirus 5 Alpha Merkel cell polyomavirus MCPyV NC_010277 2008
Merkel cell cancer[5]
[45][11][46]
Human polyomavirus 8 Alpha Trichodysplasia spinulosa polyomavirus TSPyV NC_014361 2010 Trichodysplasia spinulosa[5] [47][48]
Human polyomavirus 9 Alpha Human polyomavirus 9 HPyV9 NC_015150 2011 None known [49]
Human polyomavirus 12 Alpha
Human polyomavirus 12
HPyV12 NC_020890 2013 None known [50]
Human polyomavirus 13 Alpha New Jersey polyomavirus NJPyV NC_024118 2014 None known [51]
Human polyomavirus 1 Beta
BK polyomavirus
BKPyV NC_001538 1971 Polyomavirus-associated
haemorrhagic cystitis[5]
[52]
Human polyomavirus 2 Beta
JC polyomavirus
JCPyV NC_001699 1971 Progressive multifocal leukoencephalopathy[5] [53]
Human polyomavirus 3 Beta KI polyomavirus KIPyV NC_009238 2007 None known [54]
Human polyomavirus 4 Beta WU polyomavirus WUPyV NC_009539 2007 None known [14]
Human polyomavirus 6 Delta Human polyomavirus 6 HPyV6 NC_014406 2010 HPyV6 associated pruritic and dyskeratotic dermatosis (H6PD)[55] [31]
Human polyomavirus 7 Delta Human polyomavirus 7 HPyV7 NC_014407 2010 HPyV7-related epithelial hyperplasia[55][56][57] [31]
Human polyomavirus 10 Delta MW polyomavirus MWPyV NC_018102 2012 None known [58][59][60]
Human polyomavirus 11 Delta STL polyomavirus STLPyV NC_020106 2013 None known [61]
Human polyomavirus 14 Alpha Lyon IARC polyomavirus LIPyV NC_034253.1 2017 None known [62][63]

Deltapolyomavirus contains only the four human viruses shown in the above table. The Alpha and Beta groups contain viruses that infect a variety of mammals. The Gamma group contains the avian viruses.[4] Clinically significant disease associations are shown only where causality is expected.[5][64]

Antibodies to the monkey lymphotropic polyomavirus have been detected in humans suggesting that this virus - or a closely related virus - can infect humans.[65]

Clinical relevance

All the polyomaviruses are highly common childhood and young adult infections.

Merkel cell cancer.[11]

SV40

SV40 replicates in the kidneys of

non-Hodgkin's lymphomas,[69] accurate detection is often confounded by high levels of cross-reactivity for SV40 with widespread human polyomaviruses.[68] Most virologists dismiss SV40 as a cause for human cancers.[67][70][71]

Diagnosis

The diagnosis of polyomavirus almost always occurs after the primary infection as it is either asymptomatic or sub-clinical. Antibody assays are commonly used to detect presence of antibodies against individual viruses.[72] Competition assays are frequently needed to distinguish among highly similar polyomaviruses.[73]

In cases of progressive multifocal leucoencephalopathy (PML), a cross-reactive antibody to SV40 T antigen (commonly Pab419) is used to stain tissues directly for the presence of JC virus T antigen. PCR can be used on a biopsy of the tissue or cerebrospinal fluid to amplify the polyomavirus DNA. This allows not only the detection of polyomavirus but also which sub type it is.[74]

There are three main diagnostic techniques used for the diagnosis of the reactivation of polyomavirus in polyomavirus nephropathy (PVN): urine cytology, quantification of the viral load in both urine and blood, and a renal biopsy.[72] The reactivation of polyomavirus in the kidneys and urinary tract causes the shedding of infected cells, virions, and/or viral proteins in the urine. This allows urine cytology to examine these cells, which if there is polyomavirus inclusion of the nucleus, is diagnostic of infection.[75] Also as the urine of an infected individual will contain virions and/or viral DNA, quantitation of the viral load can be done through PCR.[76] This is also true for the blood.

Renal biopsy can also be used if the two methods just described are inconclusive or if the specific viral load for the renal tissue is desired. Similarly to the urine cytology, the renal cells are examined under light microscopy for polyomavirus inclusion of the nucleus, as well as cell lysis and viral partials in the extra cellular fluid. The viral load as before is also measure by PCR.[citation needed]

Tissue staining using a monoclonal antibody against MCV T antigen shows utility in differentiating Merkel cell carcinoma from other small, round cell tumors.[77] Blood tests to detect MCV antibodies have been developed and show that infection with the virus is widespread although Merkel cell carcinoma patients have exceptionally higher antibody responses than asymptomatically infected persons.[7][78][79][80]

Use in tracing human migration

The JC virus offers a promising genetic marker for human evolution and migration.[81] It is carried by 70–90 percent of humans and is usually transmitted from parents to offspring. This method does not appear to be reliable for tracing the recent African origin of modern humans.[citation needed]

History

Murine polyomavirus was the first polyomavirus discovered, having been reported by Ludwik Gross in 1953 as an extract of mouse leukemias capable of inducing parotid gland tumors.[82] The causative agent was identified as a virus by Sarah Stewart and Bernice Eddy, after whom it was once called "SE polyoma".[83][84][85] The term "polyoma" refers to the viruses' ability to produce multiple (poly-) tumors (-oma) under certain conditions. The name has been criticized as a "meatless linguistic sandwich" ("meatless" because both morphemes in "polyoma" are affixes) giving little insight into the viruses' biology; in fact, subsequent research has found that most polyomaviruses rarely cause clinically significant disease in their host organisms under natural conditions.[86]

Dozens of polyomaviruses have been identified and sequenced as of 2017, infecting mainly birds and mammals. Two polyomaviruses are known to infect fish, the

gilthead seabream.[88] A total of fourteen polyomaviruses are known to infect humans.[4]

References

  1. .
  2. ^ a b c d e f g "ICTV Report Polyomaviridae".
  3. ^ taxonomy. "Taxonomy browser (Polyomaviridae)". www.ncbi.nlm.nih.gov. Retrieved 19 March 2024.
  4. ^
    PMID 26923930
    .
  5. ^ .
  6. .
  7. ^ .
  8. ^ .
  9. ^ .
  10. ^ .
  11. ^ .
  12. ^ a b c d e f "Viral Zone". ExPASy. Retrieved 15 June 2015.
  13. S2CID 25800023
    .
  14. ^ .
  15. ^ a b c d e f g h International Agency for Research on Cancer (2013). "Introduction to Polyomaviruses" (PDF). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 104: 121–131.
  16. ^
    PMID 26474293
    .
  17. .
  18. ^ .
  19. ^ .
  20. .
  21. .
  22. .
  23. .
  24. .
  25. .
  26. .
  27. .
  28. .
  29. .
  30. .
  31. ^ .
  32. .
  33. .
  34. ^ "ICTV Taxonomy Website".
  35. ^ International Agency for Research on Cancer (2013). "IARC Working Group on the Evaluation of Carcinogenic Risk to Humans. Malaria and Some Polyomaviruses (SV40, BK, JC, and Merkel Cell Viruses)". IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 104.
  36. PMID 16731904
    .
  37. .
  38. ^ a b "Virus Taxonomy: 2020 Release". International Committee on Taxonomy of Viruses (ICTV). March 2021. Retrieved 10 May 2021.
  39. S2CID 46740584
    .
  40. .
  41. .
  42. .
  43. .
  44. .
  45. ^ Altman LK (18 January 2008). "Virus Is Linked to a Powerful Skin Cancer". The New York Times. Retrieved 18 January 2008.
  46. PMID 19499546
    .
  47. .
  48. .
  49. .
  50. .
  51. .
  52. .
  53. .
  54. .
  55. ^ .
  56. .
  57. .
  58. .
  59. .
  60. .
  61. .
  62. .
  63. .
  64. .
  65. .
  66. .
  67. ^ .
  68. ^ .
  69. .
  70. .
  71. .
  72. ^ .
  73. .
  74. .
  75. .
  76. .
  77. .
  78. .
  79. .
  80. .
  81. .
  82. .
  83. .
  84. .
  85. .
  86. .
  87. .
  88. .

External links