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.
Highlights
Papillomaviruses are species-specific, epitheliotropic, double-stranded DNA viruses
In this report we demonstrate that ultraviolet radiation (UVR), UVB (280 to 315 nm) assists in development of MmuPV1 dependent papillomas and associated malignant progression to squamous cell carcinomas, in immunocompetent strains of mice
Several lines of evidence support a link between UVR exposure and papillomavirus infection [22,23,26]
Summary
Papillomaviruses are species-specific, epitheliotropic, double-stranded DNA viruses. There are over 200 strains or genotypes of human papillomaviruses (HPVs) [1]. Other HPVs cause cutaneous warts, which are among the most common ailments treated by dermatologists [3,4,5,6]. They arise most frequently among children [7,8], and impose a significant burden in immunocompromised patients, amongst organ transplant recipients [9,10,11]. They are ubiquitous in nature and can persist in the skin asymptomatically for years most clearly in context of immunosuppressed patients [9,12]. A subset of cutaneous HPVs has been causally associated with skin cancer (reviewed in [9,13,14])
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