Human papillomaviruses (HPVs) are associated with a number of human malignancies including cervicalcancer, other anogenital cancers, and a subset of head and neck cancers. The goals of this research projectare to continue to further define and understand the viral functions and virusrhost interactions that mediateHPV-associated.disease, from the point of infection to development of HPV-associated malignancy. Overthe current funding period, the laboratories of Drs. Lambert and Ahlquist have made a number of importantcontributions to our understanding of HPV-associated disease, with the development of novel mouse modelsfor HPV-associated. malignancy, gene expression profiling of HPV-associated human cancers, identificationof useful biomarkers for HPV-associated cancers, development of a highly efficient means for producingHPV virion particles and its use in studies evaluating host interactions in early stages of HPV-infection, andstudies on the individual roles of HPV genes in the viral life cycle. In this new project, Drs. Lambert aridAhlquist together will characterize the nature and mechanisms of virus:host interactions in the context ofHPV infections and HPV-associated malignancy.
The specific aims are: (1) to investigate virahhostinteractions in the early steps of viral infection (i.e., binding, entry and establishment); (2) to define formechanistic and epidemiological analysis the changes in human gene and microRNA expression thatcharacterize each stage in the long progression from HPV infection to cervical cancer; and (3) to furthercharacterize mouse models for HPV-associated cervical cancer and to use these mouse models toinvestigate the role of particular cellular genes, including those identified in Aim 2, in cervical cancer. As inall other projects of this program-project grant, the results should have significant implications for diagnosis,prognosis, and/or therapy of persistent tumor virus infection and virus-associated cancers.
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