Merkel cell polyomavirus is a small DNA virus that infects human skin and is implicated in the development of Merkel cell carcinoma, a rare but aggressive neuroendocrine skin cancer.
Explanation
Merkel cell polyomavirus (MCPyV), identified in 2008, belongs to the Polyomaviridae family and has a circular double‑stranded DNA genome of about 5.4 kb. Serological studies indicate that infection is widespread, with most people acquiring the virus in childhood and remaining asymptomatic. The viral genome encodes early proteins, including large T and small T antigens, which orchestrate viral replication and interact with host tumor suppressors, and late proteins VP1, VP2 and VP3 that form the capsid. In productive infection the virus replicates episomally; however, in Merkel cell carcinoma the viral genome is clonally integrated into the host chromosome and harbors mutations that truncate the C‑terminus of the large T antigen while preserving its retinoblastoma protein‑binding domain. This truncation abrogates viral replication but allows persistent expression of oncoproteins that drive cell cycle progression and inhibit DNA repair, contributing to tumorigenesis. Factors that increase risk of Merkel cell carcinoma include advanced age, ultraviolet light exposure, fair skin and immunosuppression. The immune system normally controls MCPyV replication via T cell responses; loss of immune surveillance in transplant recipients or HIV‑infected patients increases viral load and tumour risk. Diagnosis of MCPyV‑positive tumors involves PCR detection of viral DNA and immunohistochemistry for the MCPyV large T antigen.
Clinical context and examples
Merkel cell carcinoma often presents as a rapidly growing, painless nodule on sun‑exposed skin in elderly or immunocompromised individuals. Approximately 80 % of these tumors harbour integrated MCPyV DNA and express truncated large T antigen, whereas a minority are virus‑negative and associated with high UV mutational burden. Patients receiving chronic immunosuppressive therapy, such as organ transplant recipients, have a markedly increased incidence of Merkel cell carcinoma. Studies have detected low levels of MCPyV DNA on normal skin and in respiratory secretions without disease. Research into MCPyV has led to development of serologic assays for exposure and vaccines targeting large T antigen epitopes. Treatment of Merkel cell carcinoma involves surgical excision, radiation and immune checkpoint inhibitors rather than antiviral therapy.
The discovery of Merkel cell polyomavirus provided a viral explanation for many cases of this cancer and highlighted how viral integration and oncoprotein expression can drive human tumorigenesis.
Related Terms: Merkel cell carcinoma, Polyomavirus, Oncogenesis, Large T antigen, Small T antigen