Retroviral recombination can lead to linkage of reverse-transcriptase mutations that confer increased zidovudine resistance
Author(s)
KELLAM, P
LARDER, BA
Type
Journal Article
Abstract
Genetic recombination between viral genomes has been shown to contribute to the generation of genetic diversity during retrovirus infections. The role of recombination in the development of human immunodeficiency virus type 1 (HIV-1) zidovudine resistance was investigated as a possible cause of the formation of the linked Leu-41/Tyr-215 resistance genotype. Zidovudine resistance is conferred by the presence of subsets of four or five amino acid substitutions in the HIV-1 reverse transcriptase. Zidovudine therapy of asymptomatic HIV-1-infected individuals results in the selection of drug-resistant variants that posses defined combinations of the five zidovudine resistance mutations. The linked Leu-41/Tyr-215 resistance genotype appears central to the continued development of high-level zidovudine resistance. By using genetically tagged mutant viruses, it was possible readily to select recombinant viruses from mixed infections of Leu-41 and Tyr-215 single mutants in the presence of zidovudine drup pressure. After three passages of a mixed infection in the presence of drug, 38% of clones screened were recombinant double mutants. In the absence of zidovudine selection, little change in the mixed virus populations was noted. No evidence of de novo generation of mutations at codons 41 and 215 was seen during any in vitro passage. This provides the first example of the role of retroviral recombination in the development of HIV-1 variants with increased drug resistance.
Date Issued
1995-02
Online Publication Date
2024-01-11T11:51:29Z
Date Acceptance
1995-02-01
ISSN
0022-538X
Publisher
American Society for Microbiology
Start Page
669
End Page
674
Journal / Book Title
Journal of Virology
Volume
69
Issue
2
Copyright Statement
Copyright © 1995, American Society for Microbiology. Kellam, P. and Larder, B.A., 1995. Retroviral recombination can lead to linkage of reverse transcriptase mutations that confer increased zidovudine resistance. Journal of virology, 69(2), pp.669-674.
Identifier
https://journals.asm.org/doi/10.1128/jvi.69.2.669-674.1995
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Publication Status
Published
Date Publish Online
1995-02-01