The Same Mutation That Encodes Low-level Human Immunodeficiency Virus Type 1 Resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine Confers High-level Resistance to the (-) Enantiomer of 2',3'-dideoxy-3'-thiacytidine

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1993 Jun 1

PMID 8392313

Citations 84

Authors

Q Gao

Z Gu

M A Parniak

J Cameron

N Cammack

C Boucher

M A Wainberg

Affiliations

Soon will be listed here.

Abstract

Variants of human immunodeficiency virus type 1 that display 500- to 1,000-fold resistance to the (-) enantiomer of 2'-deoxy-3'-thiacytidine and approximately 4- to 8-fold resistance to 2',3'-dideoxycytidine and 2',3'-dideoxyinosine have been generated through in vitro selection with the former compound. The polymerase regions of several of these resistant viruses shared a codon alteration at site 184 (ATG-->GTG; methionine-->valine), a mutation previously associated with low-level resistance to 2',3'-dideoxycytidine. The biological relevance of this mutation for the (-) enantiomer of 2'-deoxy-3'-thiacytidine was confirmed by site-directed mutagenesis with the HXB2-D clone of human immunodeficiency virus type 1.

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