Structural Control of Human Co-factors for Retroviral Gene Expression (NIH R01 GM117005)
Viruses such as HIV-1 use the human machinery to produce its RNA transcripts for protein expression and ultimately genomic replication. How viruses hijack cellular processes through interactions with host macromolecules is a fundamental question in biology and medicine. In this project, we investigate the molecular mechanisms for a human splicing factor, Tat-SF1 to coordinate production of Human Immunodeficiency Virus type 1 (HIV-1) RNAs. Specifically, we will determine and test biochemical and structural roles for Tat-SF1 interfaces with: (i) the human U2 small nuclear RNA of the splicesome; (ii) the SF3b155 subunit of the U2 snRNP; and (iii) HIV-1 for co-opting of the host splicing machinery. Targeting host cofactors offers an alternative strategy to develop new anti-HIV therapeutics. Results of these experiments will lay groundwork for understanding the interplay of a key host and viral process, and potential new avenues for therapeutic development.