PMID: 9557659Apr 29, 1998Paper

Relative replicative fitness of zidovudine-resistant human immunodeficiency virus type 1 isolates in vitro

Journal of Virology
P R HarriganB A Larder

Abstract

Replication of mixtures of two or more human immunodeficiency virus type 1 (HIV-1) variants would be expected to result in the eventual selection of the fittest virus due to Darwinian competition among the variants. The relative proportions of known HIV-1 variants (which may differ only by a single nucleotide from a standard "wild-type" virus, HIV-1HXB2) in mixed viral cultures were quantified by analysis of automated sequence signals of reverse transcriptase PCR products. With this method, the relative levels of replicative fitness of several zidovudine (3'-azidothymidine)-resistant HIV-1HXB2 variants were estimated under controlled in vitro conditions by measuring the rate of change in the proportions of viral variants as they replicated in cell cultures both in the presence and in the absence of drug selection pressure. These variants were engineered to contain commonly observed zidovudine resistance mutations in the HIV-1 reverse transcriptase (M41L, K70R, T215Y, and M41L+T215Y). In the absence of zidovudine, all variants tested displayed reduced replicative fitness compared to wild-type HIV-1HXB2. The order of relative fitness was wild type > K70R > T215Y = M41L+T215Y > M41L. Mixed cultures in the presence of zidovudine sh...Continue Reading

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Citations

Nov 9, 2000·Journal of Virology·A F MaréeR J De Boer
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·D R Kuritzkes
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