Merkel Cell Polyomavirus

Abstract

Merkel cell polyomavirus (MCV) is a recently discovered member of the polyomaviridae, a family of small DNA viruses that replicate in the nucleus of their host cell. MCV is one of at least 12 polyomaviruses that naturally infect humans, and furthermore one of four polyomaviruses that are known to cause severe human disease, predominantly in immunosuppressed or deficient individuals (DeCaprio and Garcea, Nat Rev Microbiol 2013;11(4):264–76; Korup et al., PLoS One 2013;8(3):e58021). Of these, MCV is of particular interest since it presently is the only human polyomavirus known to be involved in tumorigenesis. The virus was first identified in 2008 in tissue from Merkel cell carcinoma (MCC) by high throughput sequencing (Feng et al., Science 2008;319(5866):1096–100). Considerable evidence suggests that MCV is causally linked to MCC pathogenesis: Viral DNA is monoclonally integrated into the genome of the tumor cells in up to 90 % of all MCV cases, and the integrated MCV genomes furthermore harbor signature mutations that selectively abrogate viral replication while preserving cell cycle deregulating functions of the virus (Chang and Moore, Annu Rev Pathol 2012;7:123–44). Nonetheless, the development of MCC is doubtlessly a very rare complication of MCV infection, given that MCV is highly prevalent in the general population, with 44–80 % of adults displaying serum reactivity against viral antigens. What cells represent the natural reservoir of MCV infection in healthy individuals, whether the virus is potentially linked to human diseases other than MCC, and how precisely MCV infection contributes to cellular transformation during MCC pathogenesis are unresolved issues that are the subject of current research efforts.