Merkel Cell Polyomavirus Infection Can Cause Lethal Carcinoma

A benign virus normally found in the skin can lead to a type of rare, lethal skin cancer; specifically, infection by the Merkel cell polyomavirus can lead to Merkel cell carcinoma in immune-compromised individuals.

Merkel cell carcinoma, which metastasizes rapidly, is one of the most aggressive skin cancers, with a mortality rate of 33%, exceeding that of melanoma, and a 45% five-year survival rate and given these dire statistics, medical professionals are keen to find better treatments.

The Merkel cell polyomavirus is an abundant virus frequently found on healthy human skin. Excessive exposure to sunlight and ultraviolet radiation, immune suppression, and advanced age are the most important risk factors for Merkel cell carcinoma. Although the exact function of Merkel cells, found in the lower part of the skin epidermis, is unknown, they are thought to be nerve-associated cells involved in light touch sensation.

Scientists at the Perelman School of Medicine at the University of Pennsylvania (Philadelphia, PN, USA) have established a new way to investigate this type of oncogenic viral infection and identified a potential therapeutic agent against Merkel cell polyomavirus infection. The team discovered that the activation of special enzymes called matrix metalloproteinases by a cellular signaling pathway involving the WNT and β-catenin proteins stimulate Merkel cell polyomavirus infection.

These enzymes work in wound healing to re-engineer the skin as it heals. For example, if the skin is harmed by excessive sunlight, this stimulates the WNT/β-catenin signaling pathway, which in turn activates the metalloproteinase enzymes to be made. In the wound-healing process, these enzymes react and catalyze the extracellular matrix of affected cells. This could allow viruses to enter the cells of the dermis skin layer. Merkel cell polyomavirus (MCPyV) preferentially infected dermal fibroblasts in human skin.

The study also found that this study also found that the US Food and Drug Administration (FDA, Silver Springs, MD, USA) -approved drug trametinib for melanoma and other cancers blocks viral infection by stopping Merkel cell polyomavirus transcription and replication. Low doses of trametinib wiped out viral infection in the cell culture model developed. In addition, normal control cells were not affected by trametinib, giving hope to the fact that this drug might be able to be used with little side effects for reducing the viral load in immunocompromised patients and the goal of preventing the development of Merkel cell carcinoma.

Wei Liu, PhD, a senior postdoctoral fellow and co-author of the study, said, “Building on this novel cell culture model for Merkel cell polyomavirus infection, we would like to establish an animal model to elucidate the mechanisms by which Merkel cell polyomavirus infection leads to the highly aggressive Merkel cell carcinoma.” The study was published on June 8, 2106 in the journal Cell Host & Microbe.

Related Links:
Perelman School of Medicine at the University of Pennsylvania
US Food and Drug Administration