Molecular Biology and Genetics of Human Tumor Viruses

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PROJECT SUMMARY/ABSTRACT Viruses cause approximately 15% of human cancers. A viral etiology to a human cancer can have substantive consequences on its treatment and prevention. For example, many virally-caused human cancers express virally encoded products, which are potential targets for anti-viral, tumor-specific therapies. In addition, unique sets of cellular genes and pathways contribute to virally-associated cancers, many of which are currently being pursued as targets for anti-cancer therapies. This program project grant (PPG) has two major objectives: to use molecular biology and genetics to elucidate the life cycles of and transformation by human tumor viruses and to translate this understanding into the identification of targets for specific anti-viral, anti-tumor therapies. We are focused on studying human tumor viruses in three different virus families: papillomaviruses, Epstein Barr Virus, and Kaposi Sarcoma Virus. Together, these three families of viruses cause many of the virally-associated human cancers. This request for an Administrative Supplement to provide 5 months of bridge funding, until the competitive renewal is funded in early 2024 is to support 4 of the 5 projects in the current PPG (the one project left out has been sunsetted because Dr. Dan Loeb, Project Leader for Project 2, has retired). The goals of the four projects are: Project 1) to identify and characterize cellular genes that drive human papillomavirus-associated cancer and modulate viral infection; Project 3) to study the replication and inheritance of herpesviral genomes in relevant cell types using novel approaches for live cell imaging; Project 4) to characterize cellular and viral factors that regulate the switch from the latent to lytic viral state of Epstein Barr virus (EBV); and Project 5) to define drivers of EBV- associated carcinogenesis and develop novel approaches for treating these cancers and diseases caused by herpesviruses. There are three cores to this PPG that provide expertise in A) administration, statistics and bioinformatics, B) instrumentation, microscopy and histology, and C) virus engineering and production. These cores will be funded during this no cost extension period from institutional support as indicated in the cover letter.