Winslow DL, Anton E, Horlick R, Zagursky R, Tritch R, Scarnati H, Ackerman K, Otto M, Bacheler L; International Conference on AIDS.
Int Conf AIDS. 1994 Aug 7-12; 10: 33 (abstract no. 424A).
DuPont Merck Pharmaceutical Co., Wilmington, DE.
OBJECTIVE: Previously we reported the selection in tissue culture of HIV-1 variants with substitutions at amino acid 82 in PR with reduced susceptibility to C2 symmetric diols (PNAS 90:7543-7547, 1993). Our objective was to insert defined mutations into the PR gene of an infectious molecular clone of HIV-1 to determine the in vitro susceptibility of recovered virus to structurally dissimilar PR inhibitors. METHODS: Site-directed mutagenesis was used to create mutations in the PR gene of HXB2. Virus was recovered after transfection into MT-2 cells and susceptibility to PR inhibitors was determined by an RNA hybridization assay and the ACTG PBMC consensus assay. RESULTS: V82A and V82F variants displayed reduced sensitivity to P9941 (C2 symmetric diol), A80987, and XM323 but not to R031-8959. V82I was as sensitive as wild type virus to all 4 inhibitors tested. CONCLUSIONS: Variants with substitutions at amino acid 82 display reduced sensitivity to structurally dissimilar HIV PR inhibitors.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- HIV Infections
- HIV Protease
- HIV Protease Inhibitors
- HIV Seropositivity
- HIV-1
- In Vitro
- Isoleucine
- Mutagenesis, Site-Directed
- Mutation
- P 9941
- Simian Acquired Immunodeficiency Syndrome
- genetics
- reverse transcriptase, Human immunodeficiency virus 1
Other ID:
UI: 102210836
From Meeting Abstracts