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Published on: December 19, 2019
Role of Ultraviolet Radiation in Papillomavirus-Induced Disease
Aayushi Uberoi1, Satoshi Yoshida1, Ian H Frazer2
1McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
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.
Insights
Ultraviolet (UV) radiation, specifically UVB, makes wild-type mice susceptible to mouse papillomavirus (MmuPV1) infection, leading to cancer. This discovery offers insights into papillomavirus carcinogenesis and UVR
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Human papillomaviruses (HPVs) cause 5% of human cancers.
- Mouse papillomavirus (MmuPV1) in mice offers a model for HPV research.
- MmuPV1 disease is typically limited to immunodeficient mice.
Purpose of the Study:
- To investigate the effect of ultraviolet radiation (UVR) on MmuPV1 susceptibility in wild-type mice.
- To understand the role of UVR-induced immunosuppression in MmuPV1 pathogenesis.
- To explore MmuPV1 as a model for HPV carcinogenesis and UVR's role in infection.
Main Methods:
- Infection of wild-type mice with MmuPV1.
- Exposure of infected mice to UVB radiation.
- Assessment of disease progression and immune status.
Main Results:
- UVB exposure renders wild-type mice susceptible to MmuPV1.
- MmuPV1-infected, UVB-treated mice develop warts progressing to squamous cell carcinoma.
- UVB induces systemic immunosuppression correlating with MmuPV1 disease severity.
Conclusions:
- UVB radiation is a critical factor in MmuPV1-induced carcinogenesis in mice.
- MmuPV1 and UVR in mice serve as a relevant model for HPV pathogenesis and UVR's role in human cancers.
- Host immunity plays a key role in controlling papillomavirus-associated diseases.
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