Polyomaviruses

Polyomaviruses belong to Polyomaviridae family of viruses which comprises one genus, eleven species, seventeen subspecies, and nineteen unclassified members. Polyomaviruses are small DNA viruses capable of persistent infection. Presence in the upper respiratory tract may be a general property of human polyomaviruses. BKPyV, JCPyV , WUPyV, and KIPyV have also been identified in fecal specimens, which suggests their potential for transmission through the gastrointestinal (GI) tract. Two major types of particles are found in cells infected with these viruses: Virions containing viral DNA and protein, and empty capsids, or protein shells, that are noninfectious. Host cell histon proteins associate with viral DNA and form mini-chromosome-like structure.4,6,10

Polyomaviruses require the apparatus of cell DNA synthesis for their own replication. To meet this need they have evolved many different ways to intervene in cell growth regulation. This intervention can cause tumors in humans and animals. To date, five genetically distinct human polyomaviruses have been identified.



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BK polyomavirus (BKPyV) was first isolated from the urine of a patient on immunosuppressive therapy following kidney transplantation. BKPyV appears to be a common infection in humans which usually produces no symptoms. Much of this host resistance is attributed to the remarkable ability of T-cell immunity to prevent virus activation. BK polyomavirus has been associated with mild respiratory disease in children and can be detected in tonsils.1 The virus also commonly infects the urinary tract.

BK polyomavirus uses several mechanisms to induce tumors. It targets and inhibits several key cell cycle regulatory genes, including p53, a tumor suppressor gene. The virus produces a number of T-proteins, or tumor-initiating proteins. BK polyomavirus also causes structural changes in chromosomes and damages DNA repair mechanism.

Since its discovery in the early 1970s, BK polyomavirus has been isolated in a variety of human tumor cells, including prostate cancer, adrenal cancer, renal cell carcinomas, colorectal cancer, brain cancers, cervical carcinoma, genital tumors, Kaposi sarcoma, bone cancer, urinary tract tumors, and insulinoma (tumor of the pancreatic islets).3

JC polyomavirus (JCPyV) is closely related to BKPyV and simian vacuolating virus 40 (SV40). It was first isolated in 1971 from the brain tissue of a PML patient. It is estimated that 70-80% of the world population is infected with this virus early in childhood without apparent clinical symptoms. JCPyV viral DNA has also been detected in tonsils. The virus establishes a persistent infection in the kidneys and is reactivated under immunocompromised conditions.4 JCPyV infects and destroys olygodendrocytes which are myelin-producing cells in the CNS, and indirectly causes death of neurons in the white matter of the brain. The destruction of both oligodendrocytes and neurons results in PML, a neurodegenerative disease. JC polyomavirus has been implicated in the development of lung cancer, colorectal cancer, esophageal carcinoma, and brain cancers.3,5

KI polyomavirus (KIPyV) (Karolinska Institutet virus) was first isolated in 2007 from children less than 5 years of age with respiratory tract infections who had conditions ranging from a common cold to acute respiratory distress.. Primary infection with this virus occurs during childhood or youth.5,9

WU polyomavirus (WUPyV) (Washington University virus) was initially isolated in 2007 from a patient with acute respiratory tract infection. The virus has a worldwide distribution and has been detected in respiratory secretions from patients with respiratory diseases. Primary infection with this virus occurs during childhood or youth. Young children may be susceptible to infection with this virus and occasionally the infection with this virus may cause severe disease. WUPyV has been suggested to be a respiratory pathogen. The most common clinical findings are cough and wheezing.

WU polyomavirus has also been detected in specimens from the GI tract. However, it's precise role in GI disease remains unclear. WUPyV may act as an opportunistic pathogen in the GI tract, colonize the GI tract without causing any disease, or be a part of the internal viral flora that are reactivated by other viral infections. It has been suggested that WU polyomavirus can be shed for prolong periods following previous acute infection.8,9,11

So far, WUPyV infections can not be distinguished from other viral infections by means of clinical symptoms. Respiratory tract disease like pneumonia or bronchitis is frequently observed in patients harboring WUPyV.12

Merkel cell polyomavirus (MCPyV) was discovered in 2008 in Merkel cell tumor, a rare form of skin cancer. Subsequently, MCPyV has been isolated from human respiratory secretions which indicates that it is shed into the respiratory tract or present in cells of the respiratory tract, similar to KIPyV, WUPyV, BKPyV, and possibly JCPyV. However, conclusions about their primary target organs and pathogenicity can be drawn based on further investigation.6

The fact that Merkel cell polyomavirus is found in the malignant cells provides proof that this virus is directly involved in the cancer initiation process predicted by previous research with SV40 and murine PyV (MPyV). This discovery is another reminder that we certainly have not seen the end of new human polyomavirus identification, but rather the beginning of a new era.7

References

  1. The dictionary of virology. Brian W. J. Mahy
  2. Desk Encyclopedia of Human and Medical Virology. Brian W. J. Mahy, Marc H. V. van Regenmortel
  3. HPV and Other Infectious Agents In Cancer. Hans Krueger, Richard Gallagher, Gavin Stuart, Dan Williams
  4. Desk Encyclopedia of Animal and Bacterial Virology. Brian W. J. Mahy, Marc H. V. van Regenmortel
  5. Polyomaviruses KI and WU in Immunocompromised Patients with Respiratory Disease. Thomas Mourez et al.
  6. Merkel Cell Polyomavirus in Respiratory Tract Secretions. Shan Goh et al
  7. KI, WU and Merkel cell polyomaviruses: A new era for human polyomavirus research. Tina Dalianis et al.
  8. KI and WU Polyomaviruses in Children, France by Vincent Foulongne et al.
  9. High prevalence of antibodies against polyomavirus WU, polyomavirus KI, and human bocavirus in German blood donors. Florian Neske
  10. WU Polyomavirus in Fecal Specimens of Children with Acute Gastroenteritis. Lili Ren et al.
  11. Detection and clinical characterization of WU polyomavirus in acute respiratory tract infection in children by Zhuang WL et al.; 12. WU Polyomavirus (WUPyV): A Recently Detected Virus Causing Respiratory Disease? by Michael Kleines et al.



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