PMID: 7529334Feb 1, 1995Paper

Retroviral recombination can lead to linkage of reverse transcriptase mutations that confer increased zidovudine resistance

Journal of Virology
P Kellam, B A Larder

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 evid...Continue Reading

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Citations

Oct 9, 2002·The Journal of Biological Chemistry·Ricardo H RodaRobert A Bambara
Apr 18, 2003·AIDS·Rafael NájeraMichael M Thomson
May 26, 2005·Bioinformatics·Vladimir N MininMarc A Suchard
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