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

被引:30
作者
Shi, Binshan [1 ]
Kitchen, Christina [2 ]
Weiser, Barbara [1 ,3 ]
Mayers, Douglas [4 ]
Foley, Brian [5 ]
Kemal, Kimdar [1 ]
Anastos, Kathryn [6 ]
Suchard, Marc [2 ]
Parker, Monica [1 ]
Brunner, Cheryl [1 ]
Burger, Harold [1 ,3 ]
机构
[1] New York State Dept Hlth, Wadsworth Ctr, Div Infect Dis, Albany, NY 12208 USA
[2] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA
[3] Albany Med Coll, Dept Med, Albany, NY 12208 USA
[4] Idenix Pharmaceut Inc, Cambridge, MA 02139 USA
[5] Los Alamos Natl Lab, Los Alamos, NM 87545 USA
[6] Albert Einstein Coll Med, Div Gen Internal Med, Bronx, NY 10467 USA
关键词
HIV-1 drug resistance; HIV-1; recombination; tropism; HUMAN-IMMUNODEFICIENCY-VIRUS; FEMALE GENITAL-TRACT; CORECEPTOR USAGE; IN-VIVO; TYPE-1; ENV; V3; LOOP; VIROLOGICAL FAILURE; VIRAL LOAD; POL SEQUENCES; GENOMIC RNA;
D O I
10.1016/j.virol.2010.04.008
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 pot 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 similar to 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. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:5 / 20
页数:16
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