Merkel cell polyomavirus

Human polyomavirus 5
Virus classification Edit this classification
(unranked): Virus
Realm: Monodnaviria
Kingdom: Shotokuvirae
Phylum: Cossaviricota
Class: Papovaviricetes
Order: Sepolyvirales
Family: Polyomaviridae
Genus: Alphapolyomavirus
Species:
Human polyomavirus 5

Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania.[1] It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called digital transcriptome subtraction.[2] 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.[3] Approximately 80% of Merkel cell carcinoma (MCC) tumors have been found to be infected with MCV. MCV appears to be a common—if not universal—infection of older children and adults.[4][5] It is found in respiratory secretions, suggesting that it might be transmitted via a respiratory route. However, it has also been found elsewhere, such as in shedded healthy skin and gastrointestinal tract tissues, thus its precise mode of transmission remains unknown.[6][7] In addition, recent studies suggest that this virus may latently infect the human sera[8] and peripheral blood mononuclear cells.[9]

Most MCV viruses found in MCC tumors, however, have at least two mutations that render the virus nontransmissible: 1) The virus is integrated into the host genome and 2) The viral T antigen has truncation mutations that leave the T antigen unable to initiate DNA replication needed to propagate the virus.[10]

Evidence that MCV is the cause for most MCC tumors comes from studies in which T antigen oncoproteins from the virus are inhibited. Knockdown of these viral proteins causes cells from MCV-positive MCC tumors to die whereas there is no effect on cells from tumors that are uninfected with the virus.[11] This indicates that MCV is necessary to maintain the virus-positive tumor cells. Further, clonal pattern of MCV insertions into MCC cell genomes indicates that the virus was present in the Merkel cell before it underwent cancerous transformation. The IARC has recently classified MCV as a class 2A carcinogen.[12]

  1. ^ Feng H, Shuda M, Chang Y, Moore PS (February 2008). "Clonal integration of a polyomavirus in human Merkel cell carcinoma". Science. 319 (5866): 1096–100. Bibcode:2008Sci...319.1096F. doi:10.1126/science.1152586. PMC 2740911. PMID 18202256.
  2. ^ Feng H, Taylor JL, Benos PV, Newton R, Waddell K, Lucas SB, Chang Y, Moore PS (October 2007). "Human transcriptome subtraction by using short sequence tags to search for tumor viruses in conjunctival carcinoma". Journal of Virology. 81 (20): 11332–40. doi:10.1128/JVI.00875-07. PMC 2045575. PMID 17686852.
  3. ^ Rotondo JC, Bononi I, Puozzo A, Govoni M, Foschi V, Lanza G, Gafà R, Gaboriaud P, Touzé FA, Selvatici R, Martini F, Tognon M (July 2017). "Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF". Clinical Cancer Research. 23 (14): 3929–3934. doi:10.1158/1078-0432.CCR-16-2899. hdl:11392/2378829. PMID 28174236.
  4. ^ Kean JM, Rao S, Wang M, Garcea RL (March 2009). Atwood WJ (ed.). "Seroepidemiology of human polyomaviruses". PLOS Pathogens. 5 (3): e1000363. doi:10.1371/journal.ppat.1000363. PMC 2655709. PMID 19325891.
  5. ^ Tolstov YL, Pastrana DV, Feng H, Becker JC, Jenkins FJ, Moschos S, Chang Y, Buck CB, Moore PS (September 2009). "Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays". International Journal of Cancer. 125 (6): 1250–6. doi:10.1002/ijc.24509. PMC 2747737. PMID 19499548.
  6. ^ Sloots, Theo P.; Nissen, Michael D.; Whiley, David M.; Lambert, Stephen B.; Bialasiewicz, Seweryn (2009). "Merkel Cell Polyomavirus DNA in Respiratory Specimens from Children and Adults". Emerging Infectious Diseases. 15 (3): 492–4. doi:10.3201/eid1503.081067. PMC 2681122. PMID 19239774.
  7. ^ Allander, Tobias; Tiveljung-Lindell, Annika; Lindau, Cecilia; Goh, Shan (2009). "Merkel Cell Polyomavirus in Respiratory Tract Secretions". Emerging Infectious Diseases. 15 (3): 489–91. doi:10.3201/eid1503.081206. PMC 2681127. PMID 19239773.
  8. ^ Mazzoni E, Rotondo JC, Marracino L, Selvatici R, Bononi I, Torreggiani E, Touzé A, Martini F, Tognon MG (2017). "Detection of Merkel Cell Polyomavirus DNA in Serum Samples of Healthy Blood Donors". Front Oncol. 7: 294. doi:10.3389/fonc.2017.00294. PMC 5712532. PMID 29238698.
  9. ^ Tagliapietra A, Rotondo JC, Bononi I, Mazzoni E, Magagnoli F, Maritati M (2020). "Droplet-digital PCR assay to detect Merkel cell polyomavirus sequences in chorionic villi from spontaneous abortion affected females". J Cell Physiol. 235 (3): 1888–1894. doi:10.1002/jcp.29213. hdl:11392/2409453. PMID 31549405.
  10. ^ Shuda M, Feng H, Kwun HJ, Rosen ST, Gjoerup O, Moore PS, Chang Y (October 2008). "T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus". Proceedings of the National Academy of Sciences of the United States of America. 105 (42): 16272–7. Bibcode:2008PNAS..10516272S. doi:10.1073/pnas.0806526105. PMC 2551627. PMID 18812503.
  11. ^ Houben R, Shuda M, Weinkam R, Schrama D, Feng H, Chang Y, Moore PS, Becker JC (July 2010). "Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens". Journal of Virology. 84 (14): 7064–72. doi:10.1128/JVI.02400-09. PMC 2898224. PMID 20444890.
  12. ^ "Archived copy" (PDF). Archived from the original (PDF) on 2011-10-25. Retrieved 2012-07-17.{{cite web}}: CS1 maint: archived copy as title (link)