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Mmupv1 Model

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Specific Aims
Human papillomavirus (HPV) infections cause cervical cancers, and some cancers of the vulva, vagina, penis, anus, and oropharynx. Two prophylactic HPV vaccines (Gardasil® and Cervarix®) can block new infections from a subset of the most prevalent HPV types, but have shown no therapeutic effect against pre-existing diseases. No effective therapeutics exists at present, and the mechanisms of HPV-associated disease progression and cancer are not well understood.
Persistent HPV infection is the greatest risk factor for the development of malignancies. How the host defense system achieves control of viral infection remains incomplete, partially due to the lack of adequate small animal models. Our long-term goal is to understand the role of innate immunity that leads to the clearance of HPV/PV infections. The specific objective of this revised proposal is to use the newly established mouse papillomavirus (MmuPV1) model to test the central hypothesis that innate immunity plays a role in papillomavirus-induced infections. We have developed the MmuPV1 infection model with a broad tropism as well as a panel of viral and immunological reagents to aid our long-term studies. The rationale for these studies is that the MmuPV1/mouse model is an …show more content…

We hypothesize that type I IFN pathway plays a role in MmuPV1-associated infection and tumor growth. Type I IFN not only plays an essential role in defense against papillomavirus infection at any stage of the virus life cycle but also regulates multiple aspects of innate and adaptive immunity. We propose to test gene knockout mice including type I (Ifnκ-/- and IFN-αβR-) and type I plus type II (Stat1-/-) to evaluate the role of IFNs and/or their receptors in papillomavirus-associated diseases. These gene knockout mice will help us to elucidate the role of type I IFN pathways in papillomavirus-associated infection and

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