Role of Ultraviolet Radiation in Papillomavirus-Induced Disease

Abstract

Human papillomaviruses are causally associated with 5% of human cancers. The recent discovery of a papillomavirus (MmuPV1) that infects laboratory mice provides unique opportunities to study the life cycle and pathogenesis of papillomaviruses in the context of a genetically manipulatable host organism. To date, MmuPV1-induced disease has been found largely to be restricted to severely immunodeficient strains of mice. In this study, we report that ultraviolet radiation (UVR), specifically UVB spectra, causes wild-type strains of mice to become highly susceptible to MmuPV1-induced disease. MmuPV1-infected mice treated with UVB develop warts that progress to squamous cell carcinoma. Our studies further indicate that UVB induces systemic immunosuppression in mice that correlates with susceptibility to MmuPV1-associated disease. These findings provide new insight into how MmuPV1 can be used to study the life cycle of papillomaviruses and their role in carcinogenesis, the role of host immunity in controlling papillomavirus-associated pathogenesis, and a basis for understanding in part the role of UVR in promoting HPV infection in humans.

Author Summary

Epidemiological studies have implicated that ultraviolet radiation (UVR) from sunlight drive papillomavirus-induced disease in healthy as well as immunocompromised humans. In this report we demonstrate that treatment of immunocompetent mice with UVR renders them susceptible to papillomas and associated squamous cell carcinoma when infected with the recently discovered murine papillomavirus (MmuPV1). Our data further suggest UVR increases susceptibility to virally induced disease by inducing immunosuppression.