A cornucopia of human polyomaviruses

Key Points The recent discovery of nine new human polyomaviruses has reinvigorated the field of polyomavirus research. Integration of the Merkel cell polyomavirus genome into the host cell genome seems to be the major risk factor for the development of Merkel cell carcinoma, a highly lethal cancer. Polyomavirus large and small T antigens bind to and perturb numerous host cell proteins that promote cell cycle entry and viral replication. It seems that polyomaviruses infect humans ubiquitously, and they tend to cause disease in immunosuppressed individuals. The use of different host cell receptors by the different human polyomaviruses seems to dictate the pathology of these viruses. The task is now to more clearly investigate the link between these viruses and both the normal microbiome and disease. In recent years, nine new human polyomaviruses have been discovered, including Merkel cell polyomavirus, which has been linked to Merkel cell carcinoma, a lethal skin cell cancer. DeCaprio and Garcea compare and contrast these new human viruses and discuss how they might interact with their human host. During the past 6 years, focused virus hunting has led to the discovery of nine new human polyomaviruses, including Merkel cell polyomavirus, which has been linked to Merkel cell carcinoma, a lethal skin cell cancer. The discovery of so many new and highly divergent human polyomaviruses raises key questions regarding their evolution, tropism, latency, reactivation, immune evasion and contribution to disease. This Review describes the similarities and differences among the new human polyomaviruses and discusses how these viruses might interact with their human host.