page_title: Merkel cell polyomavirus
section_title: Classification
hierarchical_section_title: Merkel cell polyomavirus / Classification
caption_attribution_description: English: Created by Dr. Huichen Feng.
context_page_description: Merkel cell polyomavirus was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called digital transcriptome subtraction. MCV is one of seven currently known human oncoviruses. It is suspected to cause the majority of cases of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma tumors have been found to be infected with MCV. Three years later, a team of researchers at the Dana-Farber Cancer Institute developed an antibody that detected MCV expression in 97% of MCC tumors. MCV appears to be a common—if not universal—infection of older children and adults. It is found in respiratory secretions suggesting that it may be transmitted by a respiratory route. But it also can be found shedding from healthy skin, and in gastrointestinal tract tissues and elsewhere, and so its precise mode of transmission remains unknown. In addition, recent studies suggest that this virus may latently infect the human sera and PBMCs.
context_section_description: Polyomaviruses are small (~5400 base pair), non-enveloped, double-stranded DNA viruses. MCV is the fifth polyomavirus that infects humans to be discovered. It belongs to the murine polyomavirus group, one of the three main clades of polyomaviruses. (The group is named for murine polyomavirus, the earliest virus of the group to be discovered, and does not imply that MCV is transmitted to humans from rodents.)  Although it has been confused with the controversial SV40 virus in some blog postings, it is a completely distinct virus.
  MCV is genetically most closely related to the African green monkey lymphotropic polyomavirus (formerly known as African green monkey lymphotropic papovavirus), which is consistent with MCV coevolving with human primates.
  The prototype sequence of MCV has a 5387 base pair double-stranded DNA (dsDNA) genome and encodes characteristic polyomavirus genes from opposite strands including a large T antigen, a small T antigen (LT and sT, respectively, from early strand) and viral capsid proteins VP1 and VP2/3 genes (from late strand)  . MCV T antigen has similar features to the T antigens of other polyomaviruses, which are known oncoproteins, and is expressed in human tumors. The T antigen is a spliced gene that forms multiple different proteins depending on the splicing pattern.  Both large T and small T oncoproteins are probably needed to transform healthy cells into cancer cells, and they act by targeting tumor suppressor proteins, such as retinoblastoma protein.  The LT antigen possesses a helicase motif needed for virus replication that is deleted in MCC tumors.  Unlike for other polyomaviruses, MCV sT antigen transforms cells in vitro  by activating cap-dependent translation.
  MCV also expresses a microRNA (miRNA) known as MCV-miR-M1 from its late strand which bears perfect complementarity to LT and has been shown to negatively regulate LT expression . In addition to its role in regulating MCV LT expression and DNA replication, MCV-miR-M1 has been shown to directly target and downregulate the expression of host cell immune related transcript SP100  and its role in the establishment of long-term persistent infection has been demonstrated in vitro.
caption: A complete MCV genome was designed from multiple Merkel Cell carcinoma tumors and normal human tissues.[13]
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