Poster abstracts

Poster number 28 submitted by Christopher Jones

Insights into the chaperone function of HIV-1 Gag protein

Christopher Jones (Departments of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210), Siddhartha Datta (Retrovirus Assembly Section, HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702), Alan Rein (Retrovirus Assembly Section, HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702), Karin Musier-Forsyth (Departments of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210)

Abstract:
Human immunodeficiency virus type-1 (HIV-1) recruits and packages host cell tRNA^Lys into virions for use as a primer in reverse transcription. The specific annealing of tRNA^Lys,3 to the Primer Binding Site (PBS) on the HIV-1 genome is facilitated by HIV-1 Gag polyprotein’s potent nucleic acid chaperone activity, which is believed to reside primarily in the 55-amino acid nucleocapsid protein (NC) domain. In general, nucleic acid chaperone activity promotes the rearrangement of RNA/DNA to a thermodynamically more stable conformation. Both full-length Gag and the NC domain alone anneal the tRNA primer to the PBS in vitro, but Gag displays more potent chaperone activity than NC. Exactly how Gag’s other major structural domains, capsid (CA) and matrix (MA), contribute to its overall annealing ability is poorly understood. In this work, a series of Gag variants was constructed and tested for their ability to bind, aggregate, and anneal tRNA^Lys,3 to the viral PBS. By mutating and deleting MA, CA, and NC domains of Gag, insights were gained into HIV-1 Gag protein’s remarkable chaperone function.

Keywords: HIV, Gag, tRNA