Polyomaviridae

From Wikipedia, the free encyclopedia
  (Redirected from Polyomavirus)
Jump to: navigation, search
Polyomaviridae
Polyomavirus.jpg
Micrograph showing a polyomavirus infected cell—large (blue) cell below-center-left. Urine cytology specimen.
Virus classification
Group: Group I (dsDNA)
Family: Polyomaviridae
Genus: Avipolyomavirus

Orthopolyomavirus
Wukipolyomavirus

Species

African elephant polyomavirus 1
Athymic rat polyomavirus
Avian polyomavirus
B-lymphotropic polyomavirus
Baboon polyomavirus 1 (SA12)
Baboon polyomavirus 2
Bat polyomavirus 1
BK polyomavirus
Bornean orang-utan polyomavirus
Bovine polyomavirus
California sea lion polyomavirus
Canary polyomavirus
Chimpanzee polyomavirus
Crow polyomavirus
Cynomolgus polyomavirus
Finch polyoma virus
Goose hemorrhagic polyomavirus
Gorilla gorilla gorilla polyomavirus 1
Hamster polyomavirus
Human Polyomavirus 6
Human Polyomavirus 7
Human Polyomavirus 9
Human Polyomavirus 10
JC polyomavirus
KI polyomavirus
Mastomys polyomavirus
Merkel cell polyomavirus
Murine pneumotropic virus
Murine polyomavirus
MW polyomavirus
MX polyomavirus
Rabbit kidney vacuolating virus
Pan troglodytes verus polyomavirus 1a
Pan troglodytes verus polyomavirus 2c
Simian virus 40
Sumatran orang-utan polyomavirus
Squirrel monkey polyomavirus
Trichodysplasia spinulosa-associated polyomavirus
WU polyomavirus

Polyomaviruses are DNA-based (double-stranded DNA, ~5000 base pairs, circular genome) viruses. They are small (40–50 nanometers in diameter), and icosahedral in shape, and do not have a lipoprotein envelope. Moreover, the genome possess early and late genes, contributing to its complex transcription program. They are potentially oncogenic (tumor-causing); they often persist as latent infections in a host without causing disease, but may produce tumors in a host of a different species, or a host with an ineffective immune system. The name polyoma refers to the viruses' ability to produce multiple (poly-) tumors (-oma).

The family Polyomaviridae used to be one of two genera within the now obsolete family Papovaviridae (the other family being Papillomaviridae). The name Papovaviridae derived from three abbreviations: Pa for Papillomavirus, Po for Polyomavirus, and Va for "vacuolating". Clinically, Polyomaviridæ are relevant as they contribute to pathologies such as Progressive multifocal leukoencephalopathy (JC virus), nephropathy (BK virus), and Merkel cell cancer (Merkel cell virus).

Until recently, the family of Polyomaviridae contained only one genus (Polyomavirus). The recent expansion of known Polyomaviruses called for reclassification of the family into 3 genera: Orthopolyomavirus, Wukipolyomavirus, and Avipolyomavirus.[1]

Murine polyomavirus was the first polyomavirus discovered by Ludwik Gross in 1953.[2] Subsequently, many polyomaviruses have been found to infect birds and mammals.

For nearly 40 years, only two polyomaviruses were known to infect humans. Genome sequencing technologies have recently discovered seven additional human polyomaviruses, including one causing most cases of Merkel cell carcinoma and another associated with transplant-associated dysplasia (TSV), that are natural infections of humans. Discovery of these polyomaviruses and other new—but previously undiscovered—viruses may provide clues to the etiologies for human diseases.

Polyomaviruses have been extensively studied as tumor viruses in humans and animals, leading to fundamental insights into carcinogenesis, DNA replication and protein processing. The tumor suppressor molecule p53 was discovered, for example, as a cellular protein bound by the major oncoprotein (cancer-causing protein) T antigen made by Simian vacuolating virus 40 (SV40). The avian polyomavirus sometimes referred to as the Budgerigar fledgling disease virus is a frequent cause of death among caged birds.

History[edit]

Dr. Sarah Stewart and Dr. Bernice E. Eddy were the first to describe the polyoma virus. The virus was later named the SE Polyoma Virus in their honor.

Classification[edit]

The classification of Polyomaviruses is constantly evolving due to the explosion of newly discovered viruses. Previously, the family of Polyomaviridae was divided into three major clades (genetically-related groups)—the SV40 clade, the avian clade, and the murine polyomavirus clade:[3] Recent reclassification by the International Committee on Taxonomy of Viruses (ICTV) recommended dividing the family of Polyomaviridae into three genera:[1]

  • Genus Orthopolyomavirus (type species SV40)
  • Genus Wukipolyomavirus (type species KI polyomavirus)
  • Genus Avipolyomavirus (type species Avian polyomavirus)

Many of the known viruses have not been fully classified or have not yet been officially accepted; hence, the taxonomy of this family is on going.

Unclassified viruses[edit]

A further 12 putative species have been identified in bats.[4] These await classification.

A polyoma virus has been isolated from horses.[5] This virus appears to be related to the human and other primate polyoma viruses.

Two further polyoma viruses have been isolated from humans—STL polyomavirus and MW polyoma virus.[6][7]

A new species has been identified from vervet monkeys.[8]

Taxonomy[edit]

Genus Orthopolyomavirus (type species SV40):

Species Name Abbreviation
B-lymphotropic polyomavirus (formerly known as African green monkey polyomavirus, AGMPyV) LPyV
Baboon polyomavirus 1 (formerly known as Simian Agent 12) SA12
Bat polyomavirus (formerly known as Myotis polyomavirus, MyPyV) BatPyV
BK polyomavirus BKPyV
Bornean orang-utan polyomavirus OraPyV1
Bovine polyomavirus BPyV
California sea lion polyomavirus SLPyV
Dolphin polyomavirus 1 DolPyV
Hamster polyomavirus HaPyV
JC polyomavirus JCPyV
Merkel Cell polyomavirus MCPyV
Murine pneumotropic virus (formerly known as Kilham strain of Polyomavirus, Kilham virus, K virus) MPtV
Murine polyomavirus MPyV
Simian virus 40 (formerly known as Simian vacuolating virus 40) SV40
Squirrel monkey polyomavirus SqPyV
Sumatran orang-utan polyomavirus OraPyV2
Trichodysplasia spinuolsa-associated polyomavirus TSPyV

Other related virus that may be a member of the genus Orthopolyomavirus but has not been approved as a species:
ChPyV: Chimpanzee polyomavirus

Genus Wukipolyomavirus (type species KI polyomavirus)

Species Name Abbreviation
Human polyomavirus 6 HPyV6
Human polyomavirus 7 HPyV7
KI polyomavirus (formerly known as Karolinska Institute polyomavirus) KIPyV
WU polyomavirus (formerly known as Washington University polyomavirus) WUPyV

Genus Avipolyomavirus (type species Avian polyomavirus):

Species Name Abbreviation
Avian polyomavirus (formerly known as Budgerigar Fledgling disease Polyomavirus, BFPyV) APyV
Canary polyomavirus CaPyV
Crow polyomavirus CPyV
Finch polyomavirus FPyV
Goose Hemorrhagic polyomavirus GHPyV

Other viruses with similarities to members of the family Polyomaviridae that have not been assigned to a polyomavirus species:

Species Name Abbreviation
African elephant polyomavirus 1 AelPyV-1
Athymic rat polyomavirus RatPyV
Baboon polyomavirus 2 BPyV2
Cynomolgus polyomavirus CyPV
Gorilla gorilla gorilla polyomavirus 1 GggPyV1
Human polyomavirus 9 HPyV9
Mastomys polyomavirus (multimammate mouse – Mastomys species)  ?
Pan troglodytes verus polyomavirus 1a PtvPyV1a
Pan troglodytes verus polyomavirus 2c PtvPyV2c
Rabbit kidney vacuolating virus RKV

Genome[edit]

The genome is circular, composed of double stranded DNA and has six genes: large T, small t, viral protein 1 (VP1), viral protein 2 (VP2), and viral protein 3 (VP3) and agnoprotein. It is about 5 kilobase pairs in length. VP1-3 form the viral capsid.

Replication[edit]

Prior to genome replication, the processes of viral attachment, entry and uncoating occur. Cellular receptors for polyomaviruses are sialic acid residues of gangliosides. The attachment of polyomaviruses to host cells is mediated by viral protein 1 (VP1) via the sialic acid attachment region. This can be confirmed as anti-VP1 antibodies have been shown to prevent the binding of polyomavirus to host cells.[9]

Polyomavirus virions are subsequently endocytosed and transported first to the endoplasmatic reticulum where a conformational change occurs revealing Vp2.[citation needed] Then by an unknown mechanism the virus is exported to the nucleus.[citation needed]

Polyomaviruses replicate in the nucleus of the host. They are able to utilise the host’s machinery because the genomic structure is homologous to that of the mammalian host. Moreover, the promoter sequence of Polyomavirus' promoter sequence is a strong attractant for the host's RNAP. Viral replication occurs in two distinct phases; early and late gene expression, separated by genome replication.

Early gene expression is responsible for the synthesis of non-structural proteins. Since Polyomaviruses rely on the host to control both the gene expression, the role of the non-structural proteins is to regulate the cellular mechanisms. Close to the N terminal end of polyomavirus genome are enhancer elements which induce activation and transcription of a molecule known as the T-antigen (see SV40 Large T-antigen). Early mRNA’s, encoding T-antigen are produced by host RNA polymerase II. T-antigen autoregulates early mRNA’s, subsequently leading to elevated levels of T-antigen. At high concentrations of T-antigen, early gene expression is repressed, triggering the late phase of viral infection to begin.

Genome replication acts to separate the early and late phase gene expression. The duplicated viral genome is synthesised and processed as if it were cellular DNA, exploiting the host’s machinery. As the daughter viral DNA are synthesised they associate with cellular nucleosomes to form structures that are often referred to as "minichromosomes". In this manner the DNA is packaged more efficiently.

Late gene expression synthesises the structural proteins, responsible for the viral particle composition. This occurs during and after genome replication. As with the early gene expression products, late gene expression generates an array of proteins as a result of alternative splicing.

Within each viral protein are 'nuclear localization signals' which cause the viral proteins to amass in the nucleus. Assembly of new virus particles consequently occurs within the nucleus of the host cell[citation needed].

Release of newly synthesized polyomavirus particles exit the infected cell by one of two mechanisms. Firstly and less commonly, they are transported in cytoplasmic vacuoles to the plasma membrane, where budding occurs. More frequently, they are released when the cell lyses due to the cytotoxicity of virus particles present in the infected cell.

The Polyoma large and small T-Antigens[edit]

The large T-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.[10] This is achieved by a two prong attack of inhibiting tumor suppressing genes p53 and members of the retinoblastoma (pRB) family, and stimulating cell growth pathways by binding cellular DNA, ATPase-helicase, DNA polymerase α association, and binding of transcription preinitiation complex factors.[11] This abnormal stimulation of the cell cycle is a powerful force for oncogenic transformation.

The small T-antigen protein is also able to activate several cellular pathways that stimulate cell proliferation. Polyomavirus small T antigens commonly target protein phosphatase 2A (PP2A),[12] a key multisubunit regulator of multiple pathways including Akt, the mitogen-activated protein kinase (MAPK) pathway, and the stress-activated protein kinase (SAPK) pathway.[13][14] Merkel cell polyomavirus small T antigen encodes a unique domain, called the LT-stabilization domain (LSD), that binds to and inhibits the FBXW7 E3 ligase regulating both cellular and viral oncoproteins.[15] Unlike for SV40, the MCV small T antigen directly transforms rodent cells in vitro.[16]

The Polyoma Middle T-Antigen[edit]

The Polyoma Middle T-Antigen is used in animal breast cancer model systems like the PYMT system where it is coupled to the MMTV promoter. There it functions as an oncogene, while the tissue where the tumor develops is determined by the MMTV promoter.

Agnoprotein[edit]

The agnoprotein is a small multifunctional phospho-protein found in the late coding part of the genome. It appears to be involved in DNA replication but the exact mechanism remains unclear.[17]

Human Polyomaviruses[edit]

Several polyomaviruses have been found in humans. Four of these viruses (JC virus, BK virus, KI virus and WU virus) are closely related to SV40 and infection with these viruses can be confused with SV40 infection.[18][19] Merkel cell polyomavirus (MCV) is highly divergent from the other human polyomaviruses and is most closely related to murine polyomavirus. 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).

Virus listing[edit]

  • JC virus can infect the respiratory system, kidneys, or brain (sometimes causing the fatal progressive multifocal leukoencephalopathy in the latter case). This virus like BK virus was described in 1971.
  • BK virus produces a mild respiratory infection and can affect the kidneys of immunosuppressed transplant patients. Both of these viruses are very widespread: approximately 80 percent of the adult population in the United States have antibodies to BK and JC.
  • Two polyomaviruses, KI (Karolinska Institute)[20] and WU (Washington University)[21] viruses, are closely related to each other and have been isolated from respiratory secretions. These viruses, discovered almost simultaneously in 2007, were the first of an expanding group of polyomaviruses found to naturally infect humans beyond JCV and BKV.
  • In January 2008, a new virus, Merkel cell polyomavirus, was described and shown to cause most Merkel skin cancer.[22][23][24]
  • In 2010, three new polyomaviruses infecting skin were discovered: HPyV6 and HPyV7:[25] these two viruses are as yet not associated with human disease. Trichodysplasia spinulosa-associated polyomavirus (TSV) was discovered in the proliferative skin lesion termed trichodysplasia spinulosa seen in immunosuppressed patients.[26][26] All three of these viruses were discovered by rolling circle amplification of human skin DNA that preferentially amplifies small circular genomes, such as polyomaviruses.
  • In March 2011, a ninth polyoma virus, HPyV9, related to a monkey lymphotropic virus (LPV), was cultured from the blood of immunosuppressed patients. The finding partially explains why some humans had antisera cross-reactive with monkey LPV but none of the known human polyomaviruses cross-reacted with those patients' sera.[27]
  • In 2012, a new polyoma virus (Malawi polyomavirus—MWPyV) was isolated from the stool of a healthy child from Malawi.[7] This virus has also been isolated in St. Louis, Missouri. It appears to be highly divergent from other members of this virus family.
  • In 2012, another new polyoma virus—human polyoma virus 10—was isolated from patient with the warts, hypogammaglobulinemia, infections and myelokathexis syndrome.[28]
  • In 2012, another polyoma virus—MX polyomavirus—was isolated from stool samples.[29] This virus was isolated from samples from California, Chile and Mexico. This virus was also isolated from a respiratory tract infection in Mexico. Its potential for pathogenicity (if any) is currently unknown.
  • In 2013, a new polyoma virus (human polyomavirus 12) was found in resected liver tissue.[30] Subclinical infection with this virus appears to be common (10–20% of asymptomatic population).
  • In 2013, a new polyoma virus—STL polyomavirus—was isolated from human faeces.[31]

Clinical relevance[edit]

All the polyomaviruses are highly common childhood and young adult infections.[32] Most of these infections appear to cause little or no symptoms. These viruses are probably lifelong persistent among almost all adults. Diseases caused by human polyomavirus infections are most common among persons who become immunosuppressed by AIDS, old age or after transplantation and include Merkel cell carcinoma, PML and BK nephropathy.

In addition to its role in Merkel cell carcinoma, Merkel cell polyomavirus has been reported from a number of other conditions including non small cell lung carcinoma.,[33] cervical cancer, squamous cell cancer of the skin, Bowen's disease and basal cell carcinoma.[34][35][36][37] These putative associations await confirmation. It has also been associated with atypical fibroxanthoma.[38]

SV40[edit]

The SV40 replicates in the kidneys of monkeys without causing disease, but causes sarcomas in hamsters. It is highly controversial whether it can cause disease in humans since the virus may have been introduced into the general population in the 1950s through a contaminated polio vaccine. Thus far, no widely accepted evidence for the virus being present in human cancer has been reported although reports for it being present in pleural mesothelioma, some nonHodgkin's lymphomas and other human cancers have been published. This is confounded by the high level of cross-reactivity for SV40 with known human polyomaviruses (BK virus and JC virus) that are widespread and by common use of SV40 DNA as a near universal reagent in scientific laboratories.[19] Most virologists dismiss SV40 as a cause for human cancers.[18]

Possible association with prostate cancer[edit]

BK viral genomes have been found in benign and malignant prostate tissue.[39] It has been suggested that this virus may play a role in the development of malignancy but further work in this area is required.

Diagnosis[edit]

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.[40] Competition assays are frequently needed to distinguish among highly similar polyomaviruses.[41]

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.[42]

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.[40] 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.[43] Also as the urine of an infected individual will contain virions and/or viral DNA, quanitation of the viral load can be done through PCR.[44] 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.

Tissue staining using a monoclonal antibody against MCV T antigen shows utility in differentiating Merkel cell carcinoma from other small, round cell tumors.[45] 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.[46][47][48][49]

These viruses have been found in breast tumours.[50] The importance of this finding—if any—is not known.

Treatment[edit]

There is no known treatment for infection with these viruses. However it appears that some of fluoroquinolones may have therapeutic potential.[51]

References[edit]

  1. ^ a b Johne, R; Buck CB; Allander T; Atwood WJ; et al (2011). "Taxonomical developments in the family Polyomaviridae". Arch Virol 156 (9): 1627–1634. doi:10.1007/s00705-011-1008-x. PMID 21562881. 
  2. ^ GROSS L (June 1953). "A filterable agent, recovered from Ak leukemic extracts, causing salivary gland carcinomas in C3H mice". Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine 83 (2): 414–21. doi:10.3181/00379727-83-20376. PMID 13064287. 
  3. ^ Pérez-Losada M, Christensen RG, McClellan DA, et al. (June 2006). "Comparing phylogenetic codivergence between polyomaviruses and their hosts". Journal of Virology 80 (12): 5663–9. doi:10.1128/JVI.00056-06. PMC 1472594. PMID 16731904. 
  4. ^ Tao Y, Mang S, Conrardy C, Kuzmin IV, Recuenco S, Agwanda B, Alvarez DA, Ellison JA, Gilbert AT, Moran D, Niezgoda M, J Lindblade KA, Holmes EC, Breiman RF, Rupprecht CE, Tong S (2012) Discovery of diverse Polyomaviruses in bats and the evolutionary history of the Polyomaviridae. J Gen Virol
  5. ^ Renshaw RW, Wise AG, Maes RK, Dubovi EJ. Complete genome sequence of a polyomavirus isolated from horses" J Virol 86(16) 8903
  6. ^ Lim ES, Reyes A, Antonio M, Saha D, Ikumapayi UN, Adeyemi M, Stine OC, Skelton R, Brennan DC, Mkakosya RS, Manary MJ, Gordon JI, Wang D (2012) Discovery of STL polyomavirus, a polyomavirus of ancestral recombinant origin that encodes a unique T antigen by alternative splicing. Virology pii: S0042-6822(12)00597-1. doi:10.1016/j.virol.2012.12.005
  7. ^ a b Siebrasse EA, Reyes A, Lim ES, Zhao G, Mkakosya RS, Manary MJ, Gordon JI, Wang D (2012) Identification of MW polyomavirus, a novel polyomavirus in human stool" J Virol 86(19) 10321–6. doi:10.1128/JVI.01210-12
  8. ^ Yamaguchi H, Kobayashi S, Ishii A, Ogawa H, Nakamura I, Moonga L, Hang'ombe BM, Mweene AS, Thomas Y, Kimura T, Sawa H, Orba Y (2013) Identification of a novel polyomavirus from vervet monkeys in Zambia. J Gen Virol
  9. ^ http://www.microbiologybytes.com/virology/Polyomaviruses.html
  10. ^ White MK, Gordon J, Reiss K, et al. (December 2005). "Human polyomaviruses and brain tumors". Brain Research. Brain Research Reviews 50 (1): 69–85. doi:10.1016/j.brainresrev.2005.04.007. PMID 15982744. 
  11. ^ Kelley WL, Georgopoulos C (April 1997). "The T/t common exon of simian virus 40, JC, and BK polyomavirus T antigens can functionally replace the J-domain of the Escherichia coli DnaJ molecular chaperone". Proceedings of the National Academy of Sciences of the United States of America 94 (8): 3679–84. doi:10.1073/pnas.94.8.3679. PMC 20500. PMID 9108037. 
  12. ^ http://www.ncbi.nlm.nih.gov/pubmed/2153055
  13. ^ Sontag E, Fedorov S, Kamibayashi C, Robbins D, Cobb M, Mumby M (December 1993). "The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the map kinase pathway and induces cell proliferation". Cell 75 (5): 887–97. doi:10.1016/0092-8674(93)90533-V. PMID 8252625. 
  14. ^ Watanabe G, Howe A, Lee RJ, et al. (November 1996). "Induction of cyclin D1 by simian virus 40 small tumor antigen". Proceedings of the National Academy of Sciences of the United States of America 93 (23): 12861–6. doi:10.1073/pnas.93.23.12861. PMC 24011. PMID 8917510. 
  15. ^ http://www.tumorvirology.pitt.edu/lab%20pubs/1-s2.0-S1931312813002242-main.pdf
  16. ^ http://www.tumorvirology.pitt.edu/lab%20pubs/21841310.pdf
  17. ^ Sariyer IK, Saribas AS, White MK, Safak M (2011) Infection by agnoprotein-negative mutants of polyomavirus JC and SV40 results in the release of virions that are mostly deficient in DNA content" Virol J 8(1) 255
  18. ^ a b Poulin DL, DeCaprio JA (September 2006). "Is there a role for SV40 in human cancer?". Journal of Clinical Oncology 24 (26): 4356–65. doi:10.1200/JCO.2005.03.7101. PMID 16963733. 
  19. ^ a b zur Hausen H (December 2003). "SV40 in human cancers--an endless tale?". International Journal of Cancer 107 (5): 687. doi:10.1002/ijc.11517. PMID 14566815. 
  20. ^ Allander T, Andreasson K, Gupta S, et al. (April 2007). "Identification of a third human polyomavirus". Journal of Virology 81 (8): 4130–6. doi:10.1128/JVI.00028-07. PMC 1866148. PMID 17287263. 
  21. ^ Gaynor AM, Nissen MD, Whiley DM, et al. (May 2007). "Identification of a novel polyomavirus from patients with acute respiratory tract infections". PLoS Pathogens 3 (5): e64. doi:10.1371/journal.ppat.0030064. PMC 1864993. PMID 17480120. 
  22. ^ L Altman (2008-01-18). "Virus Is Linked to a Powerful Skin Cancer". New York Times. Retrieved 2008-01-18. 
  23. ^ Feng H, Shuda M, Chang Y, Moore PS (February 2008). "Clonal integration of a polyomavirus in human Merkel cell carcinoma". Science 319 (5866): 1096–100. doi:10.1126/science.1152586. PMC 2740911. PMID 18202256. 
  24. ^ Shuda M, Arora R, Kwun HJ, et al. (September 2009). "Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors". International Journal of Cancer 125 (6): 1243–9. doi:10.1002/ijc.24510. PMID 19499546. 
  25. ^ http://www.ncbi.nlm.nih.gov/pubmed/20542254?dopt=Abstract
  26. ^ a b http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1001024
  27. ^ http://www.ncbi.nlm.nih.gov/pubmed/7017066
  28. ^ Buck CB, Phan GQ, Raiji MT, Murphy PM, McDermott DH, McBride AA (2012) Complete genome sequence of a tenth human polyomavirus" J Virol 86(19) 10887
  29. ^ Yu G, Greninger AL, Isa P, Phan TG, Martínez MA, de la Luz Sanchez M, Contreras JF, Santos-Preciado JI, Parsonnet J, Miller S, Derisi JL, Delwart E, Arias CF, Chiu CY (2012) Discovery of a novel polyomavirus in acute diarrheal samples from children. PLoS One 7(11) e49449. doi:10.1371/journal.pone.0049449
  30. ^ Korup S, Rietscher J, Calvignac-Spencer S, Trusch F, Hofmann J, Moens U, Sauer I, Voigt S, Schmuck R, Ehlers B (2013) Identification of a novel human polyomavirus in organs of the gastrointestinal tract" PLoS One 2013;8(3) e58021. doi:10.1371/journal.pone.0058021
  31. ^ Lim ES, Reyes A, Antonio M, Saha D, Ikumapayi UN, Adeyemi M, Stine OC, Skelton R, Brennan DC, Mkakosya RS, Manary MJ, Gordon JI, Wang D (2013) Discovery of STL polyomavirus, a polyomavirus of ancestral recombinant origin that encodes a unique T antigen by alternative splicing" Virology 436(2) 295–303. doi:10.1016/j.virol.2012.12.005
  32. ^ Egli A, Infanti L, Dumoulin A, Buser A, Samaridis J, Stebler C, Gosert R, Hirsch HH. J Infect Dis. 2009 Mar 15;199(6) 837–46.
  33. ^ Hashida Y, Imajoh M, Nemoto Y, Kamioka M, Taniguchi A, Taguchi T, Kume M, Orihashi K, Daibata M (2013) Detection of Merkel cell polyomavirus with a tumour-specific signature in non-small cell lung cancer. Br J Cancer doi:10.1038/bjc.2012.567
  34. ^ Imajoh M, Hashida Y, Nemoto Y, Oguri H, Maeda N, Furihata M, Fukaya T, Daibata M (2012) Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients" Virol J 9:154. doi:10.1186/1743-422X-9-154
  35. ^ Murakami M, Imajoh M, Ikawa T, Nakajima H, Kamioka M, Nemoto Y, Ujihara T, Uchiyama J, Matsuzaki S, Sano S, Daibata M (2011) Presence of Merkel cell polyomavirus in Japanese cutaneous squamous cell carcinoma" J Clin Virol 50(1) 37–41. doi:10.1016/j.jcv.2010.09.013
  36. ^ Zur Hausen A (2009) Merkel cell polyomavirus in the pathogenesis of non-melanoma skin cancer. Pathologe 30(Suppl 2) 217–20. doi:10.1007/s00292-009-1222-4
  37. ^ Kassem A, Technau K, Kurz AK, Pantulu D, Löning M, Kayser G, Stickeler E, Weyers W, Diaz C, Werner M, Nashan D, Zur Hausen A (2009) Merkel cell polyomavirus sequences are frequently detected in nonmelanoma skin cancer of immunosuppressed patients" Int J Cancer 125(2) 356–61. doi:10.1002/ijc.24323
  38. ^ Andres C, Puchta U, Flaig MJ (2010) Detection of Merkel cell polyomavirus DNA in atypical fibroxanthoma in correlation to clinical features. Am J Dermatopathol 32(8) 799–803. doi:10.1097/DAD.0b013e3181dfcdff
  39. ^ Delbue S, Matei DV, Carloni C, Pecchenini V, Carluccio S, Villani S, Tringali V, Brescia A, Ferrante P (2013) Evidence supporting the association of polyomavirus BK genome with prostate cancer. Med Microbiol Immunol
  40. ^ a b Drachenberg CB, Hirsch HH, Ramos E, Papadimitriou JC (December 2005). "Polyomavirus disease in renal transplantation: review of pathological findings and diagnostic methods". Human Pathology 36 (12): 1245–55. doi:10.1016/j.humpath.2005.08.009. PMID 16311117. 
  41. ^ Viscidi RP, Clayman B (2006). "Serological cross reactivity between polyomavirus capsids". Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology 577: 73–84. doi:10.1007/0-387-32957-9_5. ISBN 978-0-387-29233-5. PMID 16626028. 
  42. ^ Drews K, Bashir T, Dörries K (January 2000). "Quantification of human polyomavirus JC in brain tissue and cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy by competitive PCR". Journal of Virological Methods 84 (1): 23–36. doi:10.1016/S0166-0934(99)00128-7. PMID 10644084. 
  43. ^ Nickeleit V, Hirsch HH, Binet IF, et al. (May 1999). "Polyomavirus infection of renal allograft recipients: from latent infection to manifest disease". Journal of the American Society of Nephrology 10 (5): 1080–9. PMID 10232695. 
  44. ^ Randhawa PS, Vats A, Zygmunt D, et al. (August 2002). "Quantitation of viral DNA in renal allograft tissue from patients with BK virus nephropathy". Transplantation 74 (4): 485–8. doi:10.1097/00007890-200208270-00009. PMID 12352906. 
  45. ^ Busam, Klaus J.; Jungbluth, Achim A.; Rekthman, Natasha; and nine additional authors (September 2009). "Merkel Cell Polyomavirus Expression in Merkel Cell Carcinomas and Its Absence in Combined Tumors and Pulmonary Neuroendocrine Carcinomas". Am J Surg Pathol 33 (9): 1378–1385. doi:10.1097/PAS.0b013e3181aa30a5. PMC 2932664. PMID 19609205. Retrieved March 3, 2013.  (subscription required)
  46. ^ Kean JM, Rao S, Wang M, Garcea RL (March 2009). "Seroepidemiology of human polyomaviruses". In Atwood, Walter J. PLoS Pathogens 5 (3): e1000363. doi:10.1371/journal.ppat.1000363. PMC 2655709. PMID 19325891. 
  47. ^ Tolstov YL, Pastrana DV, Feng H, et al. (September 2009). "Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays". International Journal of Cancer 125 (6): 1250–6. doi:10.1002/ijc.24509. PMC 2747737. PMID 19499548. 
  48. ^ Pastrana DV, Tolstov YL, Becker JC, Moore PS, Chang Y, Buck CB (September 2009). "Quantitation of human seroresponsiveness to Merkel cell polyomavirus". In Garcea, Robert L. PLoS Pathogens 5 (9): e1000578. doi:10.1371/journal.ppat.1000578. PMC 2734180. PMID 19750217. 
  49. ^ Carter JJ, Paulson KG, Wipf GC, et al. (November 2009). "Association of merkel cell polyomavirus-specific antibodies with merkel cell carcinoma". Journal of the National Cancer Institute 101 (21): 1510–22. doi:10.1093/jnci/djp332. PMC 2773184. PMID 19776382. 
  50. ^ Hachana M, Amara K, Ziadi S, Gacem RB, Korbi S, Trimeche M (2011) Investigation of human JC and BK polyomaviruses in breast carcinomas. Breast Cancer Res Treat
  51. ^ Sharma BN, Li R, Bernhoff E, Gutteberg TJ, Rinaldo CH (2011) Fluoroquinolones inhibit human polyomavirus BK (BKV) replication in primary human kidney cells. Antiviral Res

External links[edit]