''Polyomaviridae'' is a family of
viruses
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
whose natural
hosts
A host is a person responsible for guests at an event or for providing hospitality during it.
Host may also refer to:
Places
*Host, Pennsylvania, a village in Berks County
People
*Jim Host (born 1937), American businessman
*Michel Host ( ...
are primarily mammals and birds.
As of 2020, there are six recognized genera and 117 species, five of which are unassigned to a genus.
14 species are known to infect humans, while others, such as
Simian Virus 40
SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that has the potential to cause tumors in animals, but most often ...
, have been identified in humans to a lesser extent.
Most of these viruses are very common and typically asymptomatic in most human populations studied.
BK virus is associated with
nephropathy
Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...
in
renal transplant
Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantati ...
and non-renal solid organ transplant patients,
JC virus with
progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal viral disease characterized by progressive damage (''-pathy'') or inflammation of the white matter (''leuko-'') of the brain (''-encephalo-'') at multiple locations (''mu ...
,
and
Merkel cell virus
Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called di ...
with
Merkel cell cancer
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer occurring in about 3 people per 1,000,000 members of the population. It is also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carcino ...
.
Structure and genome
Polyomaviruses are
non-enveloped
A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes.
Numerous human pathogenic viruses in circulation are encase ...
double-stranded DNA viruses with circular
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
s of around 5000
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s. The genome is packaged in a
viral capsid
A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or ma ...
of about 40-50
nanometers
330px, Different lengths as in respect to the molecular scale.
The nanometre (international spelling as used by the International Bureau of Weights and Measures; SI symbol: nm) or nanometer (American and British English spelling differences#-re ...
in diameter, which is
icosahedral
In geometry, an icosahedron ( or ) is a polyhedron with 20 faces. The name comes and . The plural can be either "icosahedra" () or "icosahedrons".
There are infinitely many non- similar shapes of icosahedra, some of them being more symmetrica ...
in shape (T=7 symmetry).
The capsid is composed of 72 pentameric
capsomere
The capsomere is a subunit of the capsid, an outer covering of protein that protects the genetic material of a virus. Capsomeres self-assemble to form the capsid.
Subunits called protomers aggregate to form capsomeres. Various arrangements of ca ...
s of a protein called
VP1, which is capable of self-assembly into a closed icosahedron;
each pentamer of VP1 is associated with one molecule of one of the other two capsid proteins,
VP2 or VP3.
The genome of a typical polyomavirus codes for between 5 and 9
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s, divided into two
transcriptional
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules calle ...
regions called the early and late regions due to the time during infection in which they are transcribed. Each region is transcribed by the host cell's
RNA polymerase II
RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryoti ...
as a single
pre-messenger RNA
A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs a ...
containing multiple genes. The early region usually codes for two proteins, the small and large tumor antigens, produced by
alternative splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...
. The late region contains the three capsid structural proteins VP1, VP2, and VP3, produced by alternative
translational
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
start sites. Additional genes and other variations on this theme are present in some viruses: for example, rodent polyomaviruses have a third protein called
middle tumor antigen The middle tumor antigen (also called the middle T-antigen and abbreviated MTag or MT) is a protein encoded in the genomes of some polyomaviruses, which are small double-stranded DNA viruses. MTag is expressed early in the infectious cycle along wi ...
in the early region, which is extremely efficient at inducing
cellular transformation
In molecular biology and genetics, transformation is the genetic alteration of a cell resulting from the direct uptake and incorporation of exogenous genetic material from its surroundings through the cell membrane(s). For transformation to ta ...
;
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
Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regula ...
control or regulatory region containing the early and late regions'
promoters, transcriptional start sites, and the
origin of replication.
Replication and life cycle
The polyomavirus life cycle begins with entry into a
host cell
In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include a ...
. Cellular receptors for polyomaviruses are
sialic acid Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone.
The term "sialic acid" (from the Greek for saliva, - ''síalon'') was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this gr ...
residues of
glycan
The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate p ...
s, commonly
ganglioside
A ganglioside is a molecule composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (e.g. ''N''-acetylneuraminic acid, NANA) linked on the sugar chain. NeuNAc, an acetylated derivative of the carbohydrate sia ...
s. The attachment of polyomaviruses to host cells is mediated by the binding of
VP1 to sialylated glycans on the cell surface.
In some particular viruses, additional cell-surface interactions occur; for example, the
JC virus
''Human polyomavirus 2'', commonly referred to as the JC virus or John Cunningham virus, is a type of human polyomavirus (formerly known as papovavirus). It was identified by electron microscopy in 1965 by ZuRhein and Chou, and by Silverman and ...
is believed to require interaction with the
5HT2A receptor
The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations. 5-HT is sh ...
and the
Merkel cell virus
Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called di ...
with
heparan sulfate.
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.
After binding to molecules on the cell surface, the virion is
endocytosed and enters the
endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
- a behavior unique among known non-enveloped viruses
- where the viral capsid structure is likely to be disrupted by action of host cell
disulfide isomerase
Protein disulfide isomerase (), or PDI, is an enzyme in the endoplasmic reticulum (ER) in eukaryotes and the periplasm of bacteria that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as t ...
enzymes.
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
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
concentration in the cytoplasm.
Both expression of viral genes and replication of the viral genome occur in the
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
using host cell machinery. The early genes - comprising at minimum the
small tumor antigen
The small tumor antigen (also called the small T-antigen and abbreviated STag or ST) is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. STag is expressed early in the infectious cycle and is usually ...
(ST) and
large tumor antigen
The large tumor antigen (also called the large T-antigen and abbreviated LTag or LT) is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. LTag is expressed early in the infectious cycle and is essent ...
(LT) - are expressed first, from a single
alternatively spliced
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be in ...
messenger RNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the p ...
strand. These proteins serve to manipulate the host's
cell cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
- dysregulating the transition from
G1 phase
The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps leadi ...
to
S phase
S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during ...
, when the host cell's genome is replicated - because host cell DNA replication machinery is needed for viral genome replication.
The precise mechanism of this dysregulation depends on the virus; for example,
SV40 LT can directly bind host cell
p53, but
murine polyomavirus
Murine polyomavirus (also known as mouse polyomavirus, ''Polyomavirus muris'', or ''Mus musculus'' polyomavirus 1, and in older literature as SE polyoma or parotid tumor virus; abbreviated MPyV) is an unenveloped double-stranded DNA virus of the ...
LT does not.
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.
As these interactions begin, the LTs belonging to several polyomaviruses, including
Merkel cell polyomavirus
Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called d ...
, present oncogenic potential.
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,
the expression of un-terminated late mRNAs with extensions complementary to early mRNA,
and the expression of regulatory
microRNA.
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 factories.
The mechanism of viral release from the host cell varies among polyomaviruses; some express proteins that facilitate cell exit, such as the
agnoprotein or
VP4
On2 TrueMotion VP3 is a ( royalty-free) lossy video compression format and video codec. It is an incarnation of the TrueMotion video codec, a series of video codecs developed by On2 Technologies.
There is no formal specification for the VP3 bit ...
.
In some cases high levels of encapsidated virus result in cell
lysis
Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
, releasing the virions.
Viral proteins
Tumor antigens
The
large tumor antigen
The large tumor antigen (also called the large T-antigen and abbreviated LTag or LT) is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. LTag is expressed early in the infectious cycle and is essent ...
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. This is achieved by a two prong attack of inhibiting tumor suppressing genes p53 and members of the
retinoblastoma
Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively fo ...
(pRB) family, and stimulating cell growth pathways by binding cellular DNA, ATPase-helicase, DNA polymerase α association, and binding of transcription preinitiation complex factors. This abnormal stimulation of the cell cycle is a powerful force for oncogenic transformation.
The
small tumor antigen
The small tumor antigen (also called the small T-antigen and abbreviated STag or ST) is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. STag is expressed early in the infectious cycle and is usually ...
protein is also able to activate several cellular pathways that stimulate cell proliferation. Polyomavirus small T antigens commonly target protein phosphatase 2A (
PP2A
Protein phosphatase 2 (PP2), also known as PP2A, is an enzyme that in humans is encoded by the ''PPP2CA'' gene. The PP2A heterotrimeric protein phosphatase is ubiquitously expressed, accounting for a large fraction of phosphatase activity in eu ...
), a key multisubunit regulator of multiple pathways including
Akt, the mitogen-activated protein kinase (MAPK) pathway, and the stress-activated protein kinase (SAPK) pathway.
Merkel cell polyomavirus
Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called d ...
small T antigen encodes a unique domain, called the LT-stabilization domain (LSD), that binds to and inhibits the
FBXW7
F-box/WD repeat-containing protein 7 is a protein that in humans is encoded by the ''FBXW7'' gene.
Function
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F ...
E3 ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin ...
regulating both cellular and viral oncoproteins. Unlike for SV40, the MCV small T antigen directly transforms rodent cells in vitro.
The
middle tumor antigen The middle tumor antigen (also called the middle T-antigen and abbreviated MTag or MT) is a protein encoded in the genomes of some polyomaviruses, which are small double-stranded DNA viruses. MTag is expressed early in the infectious cycle along wi ...
is used in
model organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
s developed to study cancer, such as the
MMTV-PyMT
Breast cancer metastatic mouse models are experimental approaches in which mice are genetically manipulated to develop a mammary tumor leading to distant focal lesions of mammary epithelium created by metastasis. Mammary cancers in mice can be ca ...
system where middle T 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.
Capsid proteins
The polyomavirus capsid consists of one major component,
major capsid protein VP1
Major capsid protein VP1 is a viral protein that is the main component of the polyomavirus capsid. VP1 monomers are generally around 350 amino acids long and are capable of self-assembly into an icosahedral structure consisting of 360 VP1 molecule ...
, and one or two minor components,
minor capsid proteins VP2 and VP3
Minor capsid protein VP2 and minor capsid protein VP3 are viral proteins that are components of the polyomavirus capsid. Polyomavirus capsids are composed of three proteins; the major component is major capsid protein VP1, which self-assembles int ...
. VP1
pentamer
A pentamer is an entity composed of five sub-units.
In chemistry, it applies to molecules made of five monomers.
In biochemistry, it applies to macromolecules, in particular to pentameric proteins, made of five proteic sub-units.
In microbiolog ...
s form the closed
icosahedral
In geometry, an icosahedron ( or ) is a polyhedron with 20 faces. The name comes and . The plural can be either "icosahedra" () or "icosahedrons".
There are infinitely many non- similar shapes of icosahedra, some of them being more symmetrica ...
viral capsid
A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or ma ...
, and in the interior of the capsid each pentamer is associated with one molecule of either VP2 or VP3.
Some polyomaviruses, such as
Merkel cell polyomavirus
Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called d ...
, do not encode or express VP3.
The capsid proteins are expressed from the late region of the genome.
Agnoprotein
The
agnoprotein is a small multifunctional phospho-protein found in the late coding part of the genome of some polyomaviruses, most notably
BK virus
The BK virus is a member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon, with the exception of the immunocompromised and the immunosuppressed. BK virus is an abb ...
,
JC virus
''Human polyomavirus 2'', commonly referred to as the JC virus or John Cunningham virus, is a type of human polyomavirus (formerly known as papovavirus). It was identified by electron microscopy in 1965 by ZuRhein and Chou, and by Silverman and ...
, 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.
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
papillomaviruses, which share many structural features but have very different genomic organizations, were classified together in the now-obsolete family ''
Papovaviridae
''Papovaviricetes'' is a class of viruses. The class shares the name of an abolished family, ''Papovaviridae'', which was split in 1999 into the two families ''Papillomaviridae'' and ''Polyomaviridae''. The class was established in 2019 and takes ...
''.
(The name ''Papovaviridae'' derived from three abbreviations: Pa for ''Papillomavirus'', Po for ''Polyomavirus'', and Va for "vacuolating.")
The polyomaviruses were divided into three major
clade
A clade (), also known as a monophyletic group or natural group, is a group of organisms that are monophyletic – that is, composed of a common ancestor and all its lineal descendants – on a phylogenetic tree. Rather than the English term, ...
s (that is, genetically-related groups): the SV40 clade, the avian clade, and the murine polyomavirus clade. A subsequent proposed reclassification by the
International Committee on Taxonomy of Viruses (ICTV) recommended dividing the family of Polyomaviridae into three genera:
* Genus ''Orthopolyomavirus'' (type species
SV40)
* Genus ''Wukipolyomavirus'' (type species
KI polyomavirus
KI polyomavirus (also known as KI virus, KIPyV, or Human polyomavirus 3) is a virus of the family Polyomaviridae. It was discovered in 2007 in stored samples of human respiratory secretions collected by the Karolinska Institute, after which the v ...
)
* 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:
* ''
Alphapolyomavirus''
* ''
Betapolyomavirus''
* ''
Deltapolyomavirus''
* ''
Epsilonpolyomavirus''
* ''
Gammapolyomavirus''
* ''
Zetapolyomavirus''
The following species are unassigned to a genus:
* ''
Centropristis striata polyomavirus 1''
* ''
Rhynchobatus djiddensis polyomavirus 1
''Rhynchobatus'' is a group of rays commonly known as wedgefishes in the family Rhinidae. They are found in the tropical and subtropical Indo-Pacific with a single species (''R. luebberti'') in the eastern Atlantic. All species in this genus are ...
''
* ''
Sparus aurata polyomavirus 1''
* ''
Trematomus bernacchii polyomavirus 1''
* ''
Trematomus pennellii polyomavirus 1
''Trematomus'' is a genus of marine ray-finned fishes, belonging to the family Nototheniidae, the notothens or cod icefishes. These fishes occur in the Southern Ocean.
Taxonomy
''Trematomus'' was first described as a genus in 1902 by the Belgian ...
''
Description of additional viruses is ongoing. These include the sea otter polyomavirus 1
and Alpaca polyomavirus
Another virus is the giant panda polyomavirus 1.
Another virus has been described from sigmodontine rodents.
Another - tree shrew polyomavirus 1 - has been described in the tree shrew.
Human polyomaviruses
Most polyomaviruses do not infect humans. Of the polyomaviruses cataloged as of 2017, a total of 14 were known with human hosts.
However, some polyomaviruses are associated with human disease, particularly in
immunocompromised individuals. 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).
A fourteenth virus has been described.
Lyon IARC polyomavirus is related to raccoon polyomavirus.
List of human polyomaviruses
The following 14 polyomaviruses with human hosts had been identified and had their
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
s sequenced as of 2017:
''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.
Clinically significant disease associations are shown only where causality is expected.
Antibodies to the monkey lymphotropic polyomavirus have been detected in humans suggesting that this virus - or a closely related virus - can infect humans.
Clinical relevance
All the polyomaviruses are highly common childhood and young adult infections.
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
immunocompromised people; disease associations include
BK virus
The BK virus is a member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon, with the exception of the immunocompromised and the immunosuppressed. BK virus is an abb ...
with
nephropathy
Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...
in
renal transplant
Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantati ...
and non-renal solid organ transplant patients,
JC virus
''Human polyomavirus 2'', commonly referred to as the JC virus or John Cunningham virus, is a type of human polyomavirus (formerly known as papovavirus). It was identified by electron microscopy in 1965 by ZuRhein and Chou, and by Silverman and ...
with
progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal viral disease characterized by progressive damage (''-pathy'') or inflammation of the white matter (''leuko-'') of the brain (''-encephalo-'') at multiple locations (''mu ...
,
and
Merkel cell virus
Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called di ...
(MCV) with
Merkel cell cancer
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer occurring in about 3 people per 1,000,000 members of the population. It is also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carcino ...
.
SV40
SV40 replicates in the kidneys of
monkey
Monkey is a common name that may refer to most mammals of the infraorder Simiiformes, also known as the simians. Traditionally, all animals in the group now known as simians are counted as monkeys except the apes, which constitutes an incomple ...
s without causing disease, but can cause cancer in rodents under laboratory conditions. In the 1950s and early 1960s, well over 100 million people may have been exposed to SV40 due to previously undetected SV40 contamination of
polio vaccine, prompting concern about the possibility that the virus might cause disease in humans.
Although it has been reported as present in some human cancers, including
brain tumor
A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and seconda ...
s,
bone tumor
A bone tumor is an abnormal growth of tissue in bone, traditionally classified as noncancerous (benign) or cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body such as from lung, breast, thyroi ...
s,
mesothelioma
Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall. Less commonly the lining ...
s, and
non-Hodgkin's lymphomas,
accurate detection is often confounded by high levels of cross-reactivity for SV40 with widespread human polyomaviruses.
[ Most virologists dismiss SV40 as a cause for human cancers.]
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. Competition assays are frequently needed to distinguish among highly similar polyomaviruses.
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
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
to amplify the polyomavirus DNA. This allows not only the detection of polyomavirus but also which sub type it is.
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.
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. 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. 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. 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.
Use in tracing human migration
The JC virus offers a promising genetic marker for human evolution and migration. 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
In paleoanthropology, the recent African origin of modern humans, also called the "Out of Africa" theory (OOA), recent single-origin hypothesis (RSOH), replacement hypothesis, or recent African origin model (RAO), is the dominant model of the ...
.
History
Murine polyomavirus
Murine polyomavirus (also known as mouse polyomavirus, ''Polyomavirus muris'', or ''Mus musculus'' polyomavirus 1, and in older literature as SE polyoma or parotid tumor virus; abbreviated MPyV) is an unenveloped double-stranded DNA virus of the ...
was the first polyomavirus discovered, having been reported by Ludwik Gross in 1953 as an extract of mouse leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
s capable of inducing parotid gland tumors. The causative agent was identified as a virus by Sarah Stewart and Bernice Eddy
Bernice Eddy (September 30, 1903–May 24, 1989) was an American virologist and epidemiologist. She and Sarah Elizabeth Stewart are known for their discoveries related to polyomavirus, particularly SV40 polyomavirus.
Personal life and education ...
, after whom it was once called "SE polyoma". 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 morpheme
A morpheme is the smallest meaningful Constituent (linguistics), constituent of a linguistic expression. The field of linguistics, linguistic study dedicated to morphemes is called morphology (linguistics), morphology.
In English, morphemes are ...
s 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.
Dozens of polyomaviruses have been identified and sequenced as of 2017, infecting mainly birds and mammals. Two polyomaviruses are known to infect fish, the black sea bass and gilthead seabream
The gilt-head (sea) bream (''Sparus aurata''), known as Orata in antiquity and still today in Italy and Tunisia (known as "Dorada" in Spain, "Dourada" in Portugal and "Dorade Royale" in France), is a fish of the bream family Sparidae found in th ...
. A total of fourteen polyomaviruses are known to infect humans.
References
External links
ICTV Report: Polyomaviridae
ICTV
{{Authority control
Infectious causes of cancer
Virus families