Human polyomaviruses and cancer: an overview

Abstract

The name of the family Polyomaviridae, derives from the early observation that cells infected with murine polyomavirus induced multiple (poly) tumors (omas) in immunocompromised mice. Subsequent studies showed that many members of this family exhibit the capacity of mediating cell transformation and tumorigenesis in different experimental models. The transformation process mediated by these viruses is driven by viral pleiotropic regulatory proteins called T (tumor) antigens. Similar to other viral oncoproteins T antigens target cellular regulatory factors to favor cell proliferation, immune evasion and downregulation of apoptosis. The first two human polyomaviruses were isolated over 45 years ago. However, recent advances in the DNA sequencing technologies led to the rapid identification of additional twelve new polyomaviruses in different human samples. Many of these viruses establish chronic infections and have been associated with conditions in immunosuppressed individuals, particularly in organ transplant recipients. This has been associated to viral reactivation due to the immunosuppressant therapy applied to these patients. Four polyomaviruses namely, Merkel cell polyomavirus (MCPyV), Trichodysplasia spinulosa polyomavirus (TSPyV), John Cunningham Polyomavirus (JCPyV) and BK polyomavirus (BKPyV) have been associated with the development of specific malignant tumors. However, present evidence only supports the role of MCPyV as a carcinogen to humans. In the present review we present a summarized discussion on the current knowledge concerning the role of MCPyV, TSPyV, JCPyV and BKPyV in human cancers.

Figure 1

Timeline of the discovery of human polyomaviruses. The timeline shows the name of the virus, the year of discovery and the type of sample from which the virus was isolated. For complete references, see the text. BKV or BKPyV, human polyomavirus BK or human polyomavirus 1; JCV or JCPyV, John Cunningham or JC polyomavirus or human polyomavirus 2; KIPyV, Karolinska Institute polyomavirus or human polyomavirus 3; WUPyV, Washington University polyomavirus or human polyomavirus 4; MCPyV, Merkel cell polyomavirus or human polyomavirus 5; HPyV6, human polyomavirus 6; HPyV7, human polyomavirus 7; TSPyV, Trichodysplasia spinulosa polyomavirus or human polyomavirus 8; HPyV9, human polyomavirus 9; MWPyV, Malawi polyomavirus or human polyomavirus 10; STLPyV Saint Louis polyomavirus or human polyomavirus 11; HPyV12, human polyomavirus 12; NJPyV, New Jersey polyomavirus or human polyomavirus 13; LIPyV, Lyon IARC polyomavirus or human polyomavirus 14.

Figure 2

Schematic representation of the genomes of BKPyV, JCK, MCPyV and TSPvV. The early and late regions (gray) are transcribed from opposite strands of the genome. The early region is transcribed in the counterclockwise direction and harbors the genes coding for the different T antigen isoforms as indicated. The late region expresses the structural genes (VPs) and the agnoprotein ORF (when present). BKPyV, JCV and MCPyV express a microRNA from the opposite strand of the early region. The noncoding control region (NCCR) contains the origin of genome replication and the promoters for the regulation of transcription. For details, see text.