Date Published: May 31, 2016
Publisher: Public Library of Science
Author(s): Aayushi Uberoi, Satoshi Yoshida, Ian H. Frazer, Henry C. Pitot, Paul F. Lambert, Denise A. Galloway.
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.
Papillomaviruses are species-specific, epitheliotropic, double-stranded DNA viruses. There are over 200 strains or genotypes of human papillomaviruses (HPVs) . Mucosotropic HPVs are the most common sexually transmitted pathogens, and a subset of these viruses cause 5% of human cancers, including cervical cancer, other anogenital cancers, and a growing fraction of head and neck cancers (reviewed in ). Other HPVs cause cutaneous warts, which are among the most common ailments treated by dermatologists [3–6]. They arise most frequently among children [7,8], and impose a significant burden in immunocompromised patients, particularly amongst organ transplant recipients [9–11]. 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 also has been causally associated with skin cancer (reviewed in [9,13,14]).
The lack of infection models in a tractable laboratory animal has limited our ability to study the pathogenesis of papillomaviruses in their natural hosts. The murine papillomavirus, MmuPV1, isolated from cutaneous warts arising on immunodeficient NCR-FoxN1nu/nu laboratory mice [15,16] is a valuable animal papillomavirus because it provides us, for the first time, the opportunity to study papillomavirus infections in the context of a genetically manipulatable host.