Polyomaviruses and Papillomaviruses

Abstract

Both polyomavirus and papillomavirus families contain a small, circular DNA genome that replicates in the nucleus of infected cells. Both family members were isolated from a wide variety of species, including humans, monkeys, hamsters, mice, and birds. Historically, both family members were grouped together to form the papovavirus family, but the genomic sequencing of viruses from each family revealed that papillomavirus family members are larger in size and their genome is only transcribed from one strand of the genome in clockwise direction, whereas the expression of polyomavirus genome is bidirectional. These differences have led to both families being separated. Some family members from each group are associated with a particular disease in humans. JC virus (JCV), for example, a member of human polyomavirus family infects more than 70–80% of the human population worldwide causing central nervous system (CNS) white matter disease in immunocompromised individuals, such as AIDS patients, known as progressive multifocal leucoencephalopathy (PML). In PML patients, the virus specifically infects the oligodentrocytes in the CNS, which form the myelin sheet around the axons of neuronal cells. BK virus (BKV), another human polyomavirus, is reactivated mainly in the kidneys in those individuals who are undergoing immunosuppressive therapies, such as kidney transplant patients. In those individuals, BKV lytically infects the kidney epithelial cells and leads to compromises in the function of the organ, which is a medical condition that is described as ‘polyomavirus-associated nephropathy’ (PVAN). Simian virus 40 (SV40) is a prototype of polyomaviruses, does not cause a known human disease but has been used as a tool to understand many fundamental aspects of molecular biology and cancer, including DNA replication, transcription, RNA splicing and cell transformation. There are reported cases suggesting that SV40 might be associated with some human tumors as is the case for JCV and BKV. Papillomavirus family members also infect humans (HPVs) and more than 100 genotypes were isolated to date. However, two genotypes in particular, HPV 16 and HPV 18, appear to be clinically important due to their apparent cause of cervical cancer in women. The progression of the replication cycle of the HPV is tightly regulated by the differentiation stages of the basal epithelial cells after initial infection. Since the discovery of the first human polyomavirus, JCV, there has been a rapid expansion in the discovery of the additional human polyomaviruses bringing the present number to 13. Only two of the recently discovered human polyomaviruses, MCPyV and TSPyV have been shown to be associated with a particular disease, Merkel Cell Carcinoma and Trichodysplasia Spinulosa respectively. The rest of the human polyomaviruses, including KIPyV, WUPyV, HPyV6, HPyV7, HPyV9, HPyV10, MWPyV, MXPyV, and HPyV12 have yet to be definitively linked to with a particular human disease. In this chapter, particular attention was devoted to the description of the biology of JCV, BKV, SV40, MCPyV, TSPyV, and HPV.