Polyomaviridae is a family of viruses whose natural hosts are primarily mammals and birds.
There are 89 recognized species in this family contained within four genera, as well as 9 species that could not be assigned to a genus.
13 species are known to infect humans.
These viruses are probably lifelong persistent among almost all adults.
Most polyoma viruses, such as BK virus and JC virus, are very common and typically asymptomatic in most human populations studied.
Some polyomaviruses are associated with human diseases, particularly in immunocompromised patients.
BK virus is associated with nephropathy in organ transplant patients.
JC virus is associated with progressive multifocal leukoencephalopathy.
The Merkel cell virus is associated with Merkel cell cancer.
Some polyoma viruses are oncoviruses, meaning they can cause tumors.
Oncoviruses often persist as latent infections in a host without causing disease, but may produce tumors in a host of a different species, or in individuals with ineffective immune systems.
Unenveloped double-stranded DNA viruses with circular genomes of around 5000 base pairs.
The polyomavirus life cycle begins with entry into a host cell.
After binding to molecules on the cell surface, the virion is endocytosed and enters the endoplasmic reticulum.
It is likely the 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.
The expression of viral genes and the replication of the viral genome occur in the nucleus using host cell machinery.
These proteins serve to manipulate the host’s cell cycle , dysregulating the transition from G1 phase to S phase, and accumulation of the viral capsid proteins in the host cell cytoplasm.
The mechanism of viral release from the host cell varies among polyomaviruses.
The virus relies on the host cell machinery to replicate.
The host cell needs to be in s-phase for replication
It modulates cellular signaling pathways to stimulate progression of the cell cycle by inhibiting tumor suppressing genes p53 and members of the retinoblastoma (pRB) family.
It stimulates cell growth pathways by binding cellular DNA, ATPase-helicase, DNA polymerase association, and binding of transcription complex factors, all forces for oncogenic transformation.
Polyomavirus small T antigenscan target protein phosphatase 2A (PP2A), a key regulator of multiple pathways including Akt, the mitogen-activated protein kinase (MAPK) pathway, and the stress-activated protein kinase (SAPK) pathway.
The polyomaviruses are members of group I (dsDNA viruses).
Most polyomaviruses do not infect humans.
Many human polyomaviruses are very common and are asymptomatic.
Some polyomaviruses are associated with human disease, particularly in immunocompromised individuals.
Polyomaviruses associated with:
Merkel cell cancer
Progressive multifocal leukoencephalopathy
Common childhood and young adult infections.
Most polyomavirus infections appear to cause little or no symptoms.
Polyomavirus infections are most common among immunocompromised people.
Disease associations include BK virus with nephropathy in renal transplant and non-renal solid organ transplant patients.
JC virus is associated with progressive multifocal leukoencephalopathy.
In cases of progressive multifocal leucoencephalopathy (PML), a cross-reactive antibody to SV40 T antigen 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.
Merkel cell virus (MCV) is associated with Merkel cell cancer.
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 activation of polyomavirus in the kidneys and urinary tract causes the shedding of infected cells, virions, and/or viral proteins in the urine.
Urine can be examined for cytology to to see if there is polyomavirus inclusion of the nucleus, a diagnostic feature of infection.
The urine and blood of an infected individual will contain virions and/or viral DNA, quanitation of the viral load can be done through PCR.
Tissue staining with antibody against MCV T antigen helps to differentiate Merkel cell carcinoma from other small, round cell tumors.
Merkel cell carcinoma patients have higher MCV antibody responses than asymptomatically infected persons.
Most polyomaviruses rarely cause clinically significant disease in their host organisms under natural conditions.
Important etiology of nephropathy and graft loss in kidney transplantation patients.
Latent infection is widespread in the general population, and the presence of immunosuppression in allograft recipients can lead to reactivation of the virus and the development of a nephropathy with graft failure in 1-5% of kidney transplant recipients.
There is an association between Merkel cell polyomavirus detection and non-melanoma skin cancer in sun-exposed areas.