Doyon L, Poulin F, Pilote L, Clouette C, Thibeault D, Croteau G, Lamarre D; National Conference on Human Retroviruses and Related Infections.
Program Abstr Second Natl Conf Hum Retrovir Relat Infect Natl Conf Hum Retrovir Relat Infect 2nd 1995 Wash DC. 1995 Jan 29-Feb 2; 141.
Bio-Mega/Boehringer Ingelheim Research Incorporated, Canada.
HIV-1 protease inhibitors have been used to select protease inhibitor resistant virus variants in vitro. To date, the resistance phenotype has been associated with one or more amino acid substitutions in the protease. Here we report the in vitro selection of protease inhibitor resistant HIV-1 variants which also contain an altered cleavage site. A single nucleotide change resulting in a L leads to F substitution in the P1' position of the P7/P6 nucleocapsid cleavage site was observed. Enzymatic assays show that a peptide substrate representing this mutated cleavage F-F site is more readily cleaved by the HIV-1, HIV-2 and mutant proteases than a peptide substrate representing the wild type cleavage site F-L. We speculate that cleavage site mutations may serve to compensate for functionally compromised protease in HIV-1 protease inhibitor resistant variants. The contribution of the mutational changes in the protease and in the nucleocapsid cleavage site to the viral phenotype has been evaluated by introduction of these mutations into an HIV-1 molecular clone.
Publication Types:
Keywords:
- HIV Protease
- HIV Protease Inhibitors
- HIV-1
- HIV-2
- In Vitro
- Mutation
- Nucleocapsid
- Protease Inhibitors
- genetics
Other ID:
UI: 102213445
From Meeting Abstracts