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Virology
Aug 15, 2010;404 (1): 5-20.

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

Binshan Shi, Christina Kitchen, Barbara Weiser, Douglas Mayers, Brian Foley, Kimdar Kemal, Kathryn Anastos, Marc Suchard, Monica Parker, Cheryl Brunner, Harold Burger
Author Information
  1. Binshan Shi: Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA.
PMID: 20451945 DOI: 10.1016/j.virol.2010.04.008

Abstract

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 approximately 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.

Associated Data

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Grants

  1. R01 AI052015/NIAID NIH HHS
  2. R01 GM086887/NIGMS NIH HHS
  3. U01 AI035004/NIAID NIH HHS
  4. UO1-AI35004/NIAID NIH HHS
  5. R01-AI52015/NIAID NIH HHS

MeSH Term

Anti-HIV Agents
Antiretroviral Therapy, Highly Active
Cluster Analysis
Drug Resistance, Viral
Evolution, Molecular
Female
HIV Infections
HIV-1
Humans
Molecular Sequence Data
Phylogeny
Recombination, Genetic
Selection, Genetic
Sequence Analysis, DNA
Sequence Homology
Viral Proteins
Viral Tropism
env Gene Products, Human Immunodeficiency Virus
pol Gene Products, Human Immunodeficiency Virus

Chemicals

Anti-HIV Agents
Viral Proteins
env Gene Products, Human Immunodeficiency Virus
pol Gene Products, Human Immunodeficiency Virus
Journal Article Research Support, N.I.H., Extramural

Word Cloud

Created with Highcharts 10.0.0HIV-1resistancetropismtherapyARTevolutionpolenvrecombinationantiretroviralgenesdrugrolestrainssignificantCharacterizationresidualplasmavirushighpriorityimproveunderstandingpathogenesisunderstandviremicpatientsselectivepressureperformedlongitudinalanalysesplasma-derivedsequencessinglegenomestestedhypothesesunrelatedchangescoreceptorusageplayedviralRecombinantsidentifiedusingBayesiancomputationalmethodsHigh-levelgenotypicseenapproximately70%X4R5associationpatientdisplayedleastonerecombinantencompassingrepresentingchangepredicteddatasuggestadditionmutationcanplayshapingEvolutionencoding

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