Merkel cell polyomavirus
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Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008.[1] It is the most recently discovered human polyomavirus, and may infect 15 to 25 percent of adults, or over 1 billion people.[2] 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.
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[edit] Classification
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.[1] (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.) MCV is the only human polyomavirus discovered to date that does not fall within the SV40-like clade.[1]
MCV is genetically most closely related to the African green monkey lymphotropic polyomavirus[1] (formerly known as African green monkey lymphotropic papovavirus),[3] which is consistent with MCV coevolving with human primates.
[edit] Possible viral etiology for Merkel cell carcinoma
Merkel cell carcinoma is a highly aggressive type of skin cancer that was first described by Cyril Toker in 1972 as "trabecular tumor of the skin".[4] The cancer forms from the microscopic Merkel cell nervous organ in the skin and viscera which is responsible for touch and pressure sensation. Based on its origin, the cancer cell type is called a neuroectodermal tumor. Although rare compared with other skin cancers, the incidence of Merkel cell carcinoma in the USA tripled between 1986 and 2001, to around 1400 cases per year.[5]
Merkel cell carcinoma is mainly seen in older individuals.[5] It is known to occur at increased frequency in people with immunodeficiency, including transplant recipients and people with AIDS,[6][7] and this association suggests the possibility that a virus or other infectious agent might be involved in causing the cancer. Kaposi's sarcoma and Burkitt's lymphoma are examples of tumors known to have a viral etiology that occur at increased frequency in immunosuppressed people. Other factors associated with the development of this cancer include exposure to ultraviolet light.[5]
[edit] Discovery and characterization of MCV
Yuan Chang and Patrick S. Moore, who discovered Kaposi's sarcoma-associated herpesvirus in 1994,[8] with colleagues at the University of Pittsburgh, USA, used the novel high-throughput sequencing technique of digital transcriptome subtraction (DTS)[9] to search for the presence of a virus in Merkel cell tumors.[1] In this method, all mRNAs from a tumor are converted into cDNAs and sequenced to a depth likely to sequence a viral cDNA if it is present. The sequences are then compared with the human genome and all human sequences are "subtracted" to leave a group of sequences that are most likely nonhuman. When this was performed on four cases of Merkel cell carcinoma, one cDNA was found that was similar to sequences of known polyomaviruses but clearly distinct enough that it could be shown to be a new virus.[1] Genetic sequences from nearly 400,000 mRNAs were analyzed for the study.[2]
The prototype sequence of MCV has a 5387 base pair genome, and encodes characteristic polyomavirus genes including a large T antigen, small T antigen, VP1 and VP2/3 genes. MCV T antigen has similar features to the T antigens of other polyomaviruses, which are known oncoproteins, and is expressed in human tumors.[1]
About 80% of Merkel cell carcinoma tumors tested have been found to be infected with MCV.[1] In these tumors, the virus has integrated into the cancer cell genome and can no longer freely replicate. The tumor is said to be a "dead-end host" for the virus. Examination of infected tumors reveals that the majority have a clear monoclonal pattern, indicating that the virus integrated into a single cell before it began its cancerous expansion.[1] MCV can also be found in healthy tissues from people without Merkel cell carcinoma. While the precise prevalence of infection is unknown in humans, it is likely that most infections do not cause cancers.[10]
[edit] Prevention, diagnosis, and treatment
The authors note it is "too early to tell" whether MCV is the cause of Merkel cell carcinoma. Only a very small proportion of people infected with the virus may develop the cancer. At this time no test for the presence of the virus is generally available, nor would patients be advised to change their treatment based on knowledge of its presence. The authors will be enrolling MCC patients in research studies, but these are not likely to directly benefit participants.[11]
Moore has suggested that if his findings are confirmed, information about the virus could lead to a blood test or a vaccine that could improve the management of the disease or aid in prevention, much as the human papillomavirus vaccine can be used to prevent cervical cancer. Chang explained that study of the virus may assist in understanding other human cancers. "Once the virus integrates, it could express an oncoprotein, or it could knock out a gene that suppresses tumor growth. Either way, the results are bound to be interesting."[2] [12]
[edit] References
- ^ a b c d e f g h i Feng H, Shuda M, Chang Y, Moore PS. (2008) Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319: 1096–1100 (abstract)
- ^ a b c Newly discovered virus linked to deadly skin cancer. University of Pittsburgh Medical Center News Bureau (2007-01-17).
- ^ Pawlita M, Clad A, zur Hausen H. (1985) Complete DNA sequence of lymphotropic papovavirus: prototype of a new species of the polyomavirus genus. Virology 143: 196–211 (PMID 2998001)
- ^ Toker C. (1972) Trabecular carcinoma of the skin. Arch Dermatol 105: 107–110 (PMID 5009611)
- ^ a b c Bichakjian CK, Lowe L, Lao CD, et al. Merkel cell carcinoma: critical review with guidelines for multidisciplinary management. Cancer 110: 1–12 (PMID 17520670) (full text)
- ^ Williams RH, Morgan MB, Mathieson IM, Rabb H. (1998) Merkel cell carcinoma in a renal transplant patient: increased incidence? Transplantation 65: 1396–1397 (abstract)
- ^ Engels EA, Frisch M, Goedert JJ, et al. (2002) Merkel cell carcinoma and HIV infection. Lancet 359: 497–498 (abstract)
- ^ Chang Y, Cesarman C, Pessin MS, Lee F, et al. (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 265: 1865–1869 (PMID 7997879)
- ^ Feng H, Taylor JL, Benos PV, et al. (2007) Human transcriptome subtraction by using short sequence tags to search for tumor viruses in conjunctival carcinoma. J Virol 81: 11332–11340 (full text)
- ^ Viscidi RP, Shah KV. (2008) A skin cancer virus? Science 319: 1049–1050 (abstract)
- ^ New Pathogen Discovery:Frequently Asked Questions. KSHV laboratory, molecular virology program, University of Pittsburgh Cancer Institute. Retrieved on 2008-04-13.
- ^ Allison Gandey (2008-01-18). newly discovered virus linked to neuroendocrine cancer of the skin. MedScape Medical News.
