Project 1: Structure and dynamics of Gag maturation intermediates and mechanisms of viral genome enclosure

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P1. Abstract Virus maturation is critical for HIV-1 replication and occurs through an orchestrated series of Gag and Gag-Pol cleavages that result in formation of the conical viral capsid enclosing the viral genomic ribonucleoprotein complex. HIV-1 maturation represents an attractive target for antiviral drug development as evidenced by studies of the small molecule inhibitor bevirimat. In this project, we will employ structural, biochemical, and virological methods to generate new insights into the structure and dynamics of the immature Gag lattice and the effects of maturation inhibitors. We will also define the mechanism by which Integrase-RNA interactions localize the RNP within the viral capsid. Finally, we will dissect the mechanism by which uncleaved matrix-capsid interferes with HIV-1 maturation. These studies will reveal new fundamental aspects of HIV-1 maturation and its inhibition.