Polyomaviruses in Human Cancers: A Complex Interplay Between Environmental, Cellular, and Viral Factors

Polyomaviridae is a family of nonenveloped viruses with dsDNA genomes of approximately 5 kb. Currently, there are 6 genera (Alphapolyomavirus, Betapolyomavirus, Gammapolyomavirus, Deltapolyomavirus, Epsilonpolyomavirus, and Zetapolyomavirus) with 112 species and 6 species unassigned to a genus. Polyomaviruses have tropism for birds and mammals, although each virus has a limited host range. Human polyomavirus infections in healthy individuals have not been associated with clinical symptoms or disease. However, some conditions, such as immunosuppression, can lead to a productive infection. Most mammalian polyomaviruses are not involved in the development of cancer in their natural host. However, some viruses, such as Merkel cell polyomavirus and JCPyV, are associated with aggressive skin cancer and colon and brain cancer in immunocompromised patients, respectively. Some environmental factors may contribute to the cancer-inducing potential; although not in humans, the combination of SV40 infection and asbestos exposure is known to be linked to mesothelioma. Polyomaviruses possess oncogenic properties in cell cultures and animal models, with activity linked to the large T antigen and small T antigen proteins, through their binding to the tumor suppressors pRb and p53, and for protein phosphatase 2A, respectively. Known cellular, environmental, and viral factors associated with cancer development in a polyomavirus-infected host will be exposed.