Merkel Cell Polyomavirus

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.