924 Functional divergence of skin Human Polyomaviruses (HPyVs)

Abstract

Human Polyomaviruses (HPyV) are prevalent in many different types of tissues including skin. As its name implies, some members of this family have oncogenic potential. Merkel Cell Polyomavirus (MCPyV) plays a causative role in about 80% of Merkel Cell Carcinomas. However, other closely related HPyVs do not appear to be oncogenic. The functional differences that underlie differences in transforming potential remain unclear. The small T antigen of MCPyV has been reported to have transforming properties on mammalian cells. Here, we studied the functional properties of small T antigen from HPyV6 and 7, two other prevalent skin HPyVs, which appear to have minimal oncogenic potential, Lentiviral expression of the small T antigens from HPyV6 and 7 induced cellular senescence in primary dermal fibroblasts. HPyV6 and 7 small T transduced primary fibroblasts showed a flat and enlarged cell morphology, significantly slower cell growth rate, and high senescence associated beta galactosidase (SA-beta gal) activity. Curiously, despite the lack of a senescent phenotype, MCPyV small T increased the expression of several inflammatory cytokines, known as the senescence associated secretory phenotype (SASP), to an even greater extent than HPyV6 and 7 small T. Together, our data shows that the small T antigens of HPyV6 and 7 are functionally distinct from MCPyV and may help to explain the distinct diseases caused by the viruses. Future mechanistic study will be performed in order to address the mechanism by which this functional divergence could occur.