Polyomaviridae
Polyomaviridae | |
---|---|
Micrograph showing a polyomavirus infected cell—large (blue) cell below-center-left. Urine cytology specimen. | |
Virus classification | |
(unranked): | Virus |
Realm: | Monodnaviria |
Kingdom: | Shotokuvirae |
Phylum: | Cossaviricota |
Class: | Papovaviricetes |
Order: | Sepolyvirales |
Family: | Polyomaviridae |
Genera | |
Polyomaviridae is a family of
Structure and genome
Polyomaviruses are
The genome of a typical polyomavirus codes for between 5 and 9
Replication and life cycle
The polyomavirus life cycle begins with entry into a
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
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
The
Capsid proteins
The polyomavirus capsid consists of one major component,
Agnoprotein
The
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
- Genus Orthopolyomavirus (type species SV40)
- Genus Wukipolyomavirus (type species KI polyomavirus)
- Genus Avipolyomavirus (type species Avian polyomavirus)
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]
- Alphapolyomavirus
- Betapolyomavirus
- Deltapolyomavirus
- Epsilonpolyomavirus
- Gammapolyomavirus
- Zetapolyomavirus
The following species are unassigned to a genus:[38]
- Centropristis striata polyomavirus 1
- Rhynchobatus djiddensis polyomavirus 1
- Sparus aurata polyomavirus 1
- Trematomus bernacchii polyomavirus 1
- Trematomus pennellii polyomavirus 1
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.
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.
SV40
SV40 replicates in the kidneys of
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
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