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Host cell factors involved in retrovirus replication and disease pathogenesis


Retroviruses are relevant human pathogens affecting the lives of tens of millions of people globally each year and resulting in nearly 2 million deaths annually. Understanding the process of retrovirus infection has wide benefits including the identification of therapeutic targets to treat HIV/AIDS and better understanding of cellular pathways disrupted in diseases, such as cancer and AIDS. Here, I first present my role in a collaborative project that led to the identification of over 200 cellular factors with potentially important roles in the early stages of retrovirus infection. We identified these factors through a genome-wide siRNA screen and through characterization of interactions between host and virus proteins. Additionally, I present my work on ZASC1, a host cell transcription factor that binds to the promoter regions of both HIV-1 and MLV and regulates virus gene expression in cultured established cell lines. I generated a ZASC1 knockout mouse model, showing that this gene is non-essential to development and reproduction. This mouse model was used to characterize the role of ZASC1 in retrovirus replication and disease pathogenesis. I showed that ZASC1 influences myeloid cell differentiation in this compartment and that this transcription factor is required for efficient early Mo-MuLV infection in the bone marrow compartment. Through studies of Mo-MuLV pathogenesis in the ZASC1 knockout mouse model, I show that despite this early defect, tumorigenesis is not regulated by ZASC1

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