Polyomavirus


Polyomavirus

Taxobox



image_size = 240px
image_caption = Transmission electron micrograph of polyomavirus SV40
virus_group = i
familia = "Polyomaviridae"
genus = "Polyomavirus"
subdivision_ranks = Species
subdivision = "African green monkey polyomavirus"
"Baboon polyomavirus 2"
"BK polyomavirus"
"Bovine polyomavirus"
"Budgerigar fledgling disease virus"
"Hamster polyomavirus"
"JC polyomavirus"
"Merkel cell polyomavirus"
"Murine pneumotropic virus"
"Murine polyomavirus"
"Rabbit kidney vacuolating virus"
"Simian virus 12"
"Simian virus 40"

"Polyomavirus" is the sole genus of viruses within the family "Polyomaviridae". Polyomaviruses are DNA-based (double-stranded DNA,~5000 base pairs,circular genome), small (40-50 nanometers in diameter), and icosahedral in shape, and do not have a lipoprotein envelope. 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).

Five polyomaviruses have been found in humans. JC virus can infect the respiratory system, kidneys, or brain (sometimes causing the fatal progressive multifocal leukoencephalopathy in the latter case). 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 recently discovered polyomaviruses, KI (Karolinska Institute)cite journal |author=Allander T, Andreasson K, Gupta S, "et al" |title=Identification of a third human polyomavirus |journal=J. Virol. |volume=81 |issue=8 |pages=4130–6 |year=2007 |pmid=17287263 |doi=10.1128/JVI.00028-07 |url=http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=17287263 |accessdate=2008-01-18] and WU (Washington University)cite journal |author=Gaynor AM, Nissen MD, Whiley DM, "et al" |title=Identification of a novel polyomavirus from patients with acute respiratory tract infections |journal=PLoS Pathog. |volume=3 |issue=5 |pages=e64 |year=2007 |pmid=17480120 |doi=10.1371/journal.ppat.0030064 |url=http://pathogens.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.ppat.0030064 |accessdate=2008-01-18] viruses, are closely related to each other and have been isolated from respiratory secretions. In January 2008, a new species, Merkel cell polyomavirus, was described as the likely causative agent of Merkel skin cancer.cite news|url=http://www.nytimes.com/2008/01/18/health/research/18virus.html |title=Virus Is Linked to a Powerful Skin Cancer |publisher= New York Times |accessdate=2008-01-18 |date=2008-01-18|format= |work=|author=L Altman]

The "Simian vacuolating virus 40" replicates in the kidneys of monkeys without causing disease, but causes sarcomas in hamsters. It is unknown whether it can cause disease in humans, which has caused concern since the virus may have been introduced into the general population in the 1950s through a contaminated polio vaccine. An avian polyomavirus sometimes referred to as the "Budgerigar fledgling disease virus" is a frequent cause of death among caged birds.

The genus "Polyomavirus" used to be one of two genera within the now obsolete family "Papovaviridae" (the other genus being "Papillomavirus" which is now assigned to its own family "Papillomaviridae"). The name "Papovaviridae" derived from three abbreviations: Pa for "Papillomavirus", Po for "Polyomavirus", and Va for "vacuolating".

Replication

Prior to genome replication, the processes of viral attachment, entry and uncoating occur. Cellular receptors for polyomaviruses are currently unknown, however, attachment of polyomaviruses to host cells is mediated by viral protein 1 (VP1). This can be confirmed as anti-VP1 antibodies have been shown to prevent the binding of polyomavirus to host cells. [http://www.microbiologybytes.com/virology/Polyomaviruses.html]

Polyomavirus virions are subsequently endocytosed and transported directly to the nucleus in endocytic vacuoles where uncoating occurs.

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. 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.

"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-Antigen

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 [Martyn K. Whitea, Jennifer Gordona, Krzysztof Reissa, Luis Del Vallea, Sidney Croula, Antonio Giordanob, Armine Darbinyana, Kamel Khalili, Human polyomaviruses and brain tumors. Brain Research Reviews 50 (2005) 69 – 85] . 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 [Kelley WL, The Tyt 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. Biochemistry Vol. 94, pp. 3679–3684, April 1997] . 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 which stimulate cell proliferation. Such as the mitogen-activated protein kinase (MAPK) pathway, and the stress-activated protein kinase (SAPK) pathway [. E. Sontag, S. Fedorov, C. Kamibayashi, D. Robbins, M. Cobb, M. Mumby, The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the map kinase pathway and induces cell proliferation, Cell 75 (1993) 887– 897] [G. Watanabe, A. Howe, R.J. Lee, C. Albanese, I.W. Shu, A.N. Karnezis, L. Zon, J. Kyriakis, K. Rundell, R.G. Pestell, Induction of cyclin D1 by simian virus 40 small tumor antigen, Proc. Natl. Acad. Sci. U. S. A. 93 (1996) 12861–12866] .

The Polyoma Middle T-Antigen

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.

Diagnosis

The diagnosis of polyomavirus almost always occurs after the primary infection as it is either asymptomatic or sub-clinical. The most effective way to test whether there has been a past infection is to use haemagglutination inhibition to find if there are any corresponding antibodies to the virus [Cinthia B. Drachenberg, Hans H. Hirsch , Emilio Ramos, John C. Papadimitriou, Polyomavirus disease in renal transplantation Review of pathological findings and diagnostic method, Human Pathology (2005) 36, 1245– 1255] . This however is not necessary in immunocompetent individuals as the latent polyomavirus poses no threat.

In cases of progressive multifocal leucoencephalopathy (PML) and associated tumors, where the reactivation of polyomavirus is suspected, PCR is 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 [Drews K, Bashir K, Do¨ rries K, 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 (2000) 23–36] . ELISA-based assays for large T-Antigen and small T-Antigen are also used to detect the level of expression and thus whether reactivation has occurred [. Carbone, J. Rudzinski, M. Bocchetta, High throughput testing of the SV40 Large T antigen binding to cellular p53 identifies putative drugs for the treatment of SV40-related cancers, Virology 315 (2003) 409–414] .

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 [Cinthia B. Drachenberg, Hans H. Hirsch , Emilio Ramos, John C. Papadimitriou, Polyomavirus disease in renal transplantation Review of pathological findings and diagnostic method, Human Pathology (2005) 36, 1245– 1255] .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 [Nickeleit V, Hirsch HH, Binet IF, et al. Polyomavirus infection of renal allograft recipients: from latent infection to manifest disease. J Am Soc Nephrol 1999;10:1080] . Also as the urine of an infected individual will contain virions and/or viral DNA, quanitation of the viral load can be done done through PCR [Randhawa PS, Vats A, Zygmunt D, et al. Quantification of viral DNA in renal allograft tissue from patients with BK virus nephropathy. Transplantation 2002;74:485- 8.] . 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.

References


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Look at other dictionaries:

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  • polyomavirus — [päl΄ē ō′mə vī΄rəs] n. [ POLY + OMA] any of a genus (Polyomavirus) of papovaviruses that naturally infect wild and laboratory mice, and that cause tumors when injected into newborn mice …   English World dictionary

  • Polyomavirus — Polyomavirus,   eine Gattung der Papovaviren, deren Name Polyoma sich von der Eigenschaft, bei der Übertragung auf Versuchstiere in vielen verschiedenen Organen Tumoren erzeugen zu können, ableitet. In ihren natürlichen Wirten (Mensch, Affe,… …   Universal-Lexikon

  • Polyomavirus — Les polyomavirus font partie de la famille des Polyomaviridae[1]. Ce sont des virus dont le génome est constitué d ADN bicaténaire circulaire. Les trois virus principaux sont, chez le singe : le Simian virus 40 (SV40), et chez l humain  …   Wikipédia en Français

  • Polyomavirus — A genus of viruses (family Papovaviridae) containing DNA (MW 3 × 106), having virions about 45 nm in diameter, and including viruses oncogenic for animals; includes the polyoma virus of rodents, vacuolating viruses (SV40) of primates, and the BK… …   Medical dictionary

  • polyomavirus — noun Etymology: New Latin polyoma, from poly + oma Date: 1958 any of a family (Polyomaviridae) of double stranded DNA viruses that produce tumors in specific mammals called also polyoma …   New Collegiate Dictionary

  • polyomavirus — A DNA tumour virus with very small genome (of the Papovaviridae). Polyoma was isolated from mice, in which it causes no obvious disease, but when injected at high titre into baby rodents, including mice, causes tumours of a wide variety of… …   Dictionary of molecular biology

  • polyomavirus — noun a papovavirus that induces a wide variety of tumours in newborn animals …   Wiktionary

  • Polyomavirus — Polyo̱|ma|virus [Kunstw.] s; , ..ren (meist Mehrz.): Virus, das in verschiedenen Organen und Geweben Tumoren hervorrufen kann …   Das Wörterbuch medizinischer Fachausdrücke


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