IDENTIFICATION OF AN AMINO-ACID SUBSTITUTION IN HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 REVERSE TRANSCRIPTASE RESPONSIBLE FOR RESISTANCE TO AZIDOTHYMIDINE AND PHOSPHONOFORMATE (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

IDENTIFICATION OF AN AMINO-ACID SUBSTITUTION IN HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 REVERSE TRANSCRIPTASE RESPONSIBLE FOR RESISTANCE TO AZIDOTHYMIDINE AND PHOSPHONOFORMATE (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 33:A2179 1992. Unique Identifier : AIDSLINE ICDB/92684726
Im GJ; Tramontano E; Gonzalez CJ; Cheng YC; Dept. of Pharmacology, Yale Univ. Sch. of Medicine, New Haven, CT; 06510

Abstract: A recombinant clone of human immunodeficiency virus type 1 reverse transcriptase (RT) with reduced sensitivity to azidothymidine and phosphonoformate has been obtained from HTLV-IIIB using the polymerase chain reaction. The mutant RT retained enzyme activity and was cross-resistant to other nucleoside analogs including didehydrodeoxythymidine and dideoxycytidine, but remained sensitive to the non-nucleoside RT inhibitors BI-RG-587 and TIBO R82150. Nucleotide sequence analysis of the mutant RT revealed a single predicted amino-acid substitution (Val----Ala) at codon 90. This suggests that amino acid residue 90 is a putative component of the analog triphosphate binding site and the pyrophosphate exchange site. Substitution of alanine for valine by alanine at this site appears to produce a multidrug-resistant RT phenotype.

Keywords: Amino Acids/*GENETICS Benzodiazepines/PHARMACOLOGY Drug Resistance HIV-1/*ENZYMOLOGY Imidazoles/PHARMACOLOGY Mutation Phosphonoacetic Acid/*ANALOGS & DERIVATIVES/PHARMACOLOGY Polymerase Chain Reaction Pyridines/PHARMACOLOGY RNA-Directed DNA Polymerase/ANTAGONISTS & INHIB/*GENETICS Zalcitabine/PHARMACOLOGY Zidovudine/*PHARMACOLOGY ABSTRACT
920930
M9290904

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