1st National Conference Human Retroviruses and Related Infections Washington, DC - December 12-16, 1993

Natl Conf Hum Retrovir Relat Infect 1993 Dec 12-16;1: (abstract no. 18)

Pettit SC, Moody MD, Wehbie RS, Nantermet PV, Kaplan AH, Swanstrom R
University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

The determinants that regulate sequential proteolytic processing of the HIV-1 Gag precursor are likely to include the sequence and structural context of the processing site and the accessibility of the site to the protease. To investigate the factors that contribute to ordered processing of HIV-1 Gag, the full length Gag precursor was digested with recombinant protease in vitro. The four major processing sites in Gag were cleaved at rates that differ as much as 400- fold. Three of the four major processing sites in Gag were cleaved independently of cleavage at the other sites. The CA/p2 site, however, was cleaved approximately 20-fold faster when the downstream p2/NC site was blocked from cleavage, or when the p2 domain of Gag was deleted. Cleavage of the CA/p2 site in the full length precursor and as a peptide, was accelerated selectively by a drop in pH. The selective acceleration of the CA/p2 site at lower pH was the result of a decrease in the Km. HIV-1 virions deleted in the p2 domain of Gag had reduced infectivity despite the production of the processed final products of Gag. These results suggest that the p2 domain of HIV-1 Gag regulates sequential processing of the Gag precursor and that the presence of p2 is important for the formation of fully infectious virions.

Keywords: Acquired Immunodeficiency Syndrome, CD4-Positive T-Lymphocytes, Disease Transmission, Vertical, Female, HIV Infections, HIV Seropositivity, Humans, Infant, Longitudinal Studies, Mothers, Pregnancy, Prospective Studies, transmission

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1993-12-12
18

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