Evolution and recombination of genes encoding HIV-1 drug resistance and tropism during antiretroviral therapy

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• 作者：Binshan Shi ; Christina Kitchen ; Barbara Weiser ; Douglas Mayers ; Brian Foley ; Kimdar Kemal ; Kathryn Anastos ; Marc Suchard ; Monica Parker ; Cheryl Brunner ; Harold Burger
• 关键词：HIV-1 drug resistance ; HIV-1 recombination ; HIV-1 tropism
• 刊名：Virology
• 出版年：2010
• 出版时间：15 August 2010
• 年：2010
• 卷：404
• 期：1
• 页码：5-20
• 全文大小：2076 K

文摘

Characterization of residual plasma virus during antiretroviral therapy (ART) is a high priority to improve understanding of HIV-1 pathogenesis and therapy. To understand the evolution of HIV-1 pol and env genes in viremic patients under selective pressure of ART, we performed longitudinal analyses of plasma-derived pol and env sequences from single HIV-1 genomes. We tested the hypotheses that drug resistance in pol was unrelated to changes in coreceptor usage (tropism), and that recombination played a role in evolution of viral strains. Recombinants were identified by using Bayesian and other computational methods. High-level genotypic resistance was seen in  70 % of X4 and R5 strains during ART. There was no significant association between resistance and tropism. Each patient displayed at least one recombinant encompassing env and representing a change in predicted tropism. These data suggest that, in addition to mutation, recombination can play a significant role in shaping HIV-1 evolution.