Retroviral infection can lead to a variety of diseases including leukemias and lymphomas, solid tumors and immunosuppressive disorders in most vertebrates including humans. These diseases generally occur after long latency periods during which many rounds of viral replication occur. Therefore, understanding the mechanisms of viral assembly is important for development of therapies to treat such diseases. All viruses encoding reverse transcriptase have assembly pathways designed to sequester this enzyme into viral particles where it can only transcribe the specifically encapsidated viral genomes. This application proposes a series of experiments to understand the details of oncoretroviral genome encapsidation using the avian retrovirus, Rous sarcoma virus (RSV), as a model system. Studies will determine the structure of the packaging region of RSV RNA, which has been mapped to a 160nt contiguous sequence. In addition, regions of the viral structural protein (Gag) that are important for interaction with the packaging sequences will be defined. Recent studies in the investigator s laboratory have shown that the human foamy virus (HFV) has an assembly pathway very different from that of RSV and other conventional retroviruses. Experiments are proposed to understand how HFV packages its genome and reverse transcriptase activities. Such experiments may also reveal new commonalities with oncovirus assembly.
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