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Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome.

Publication ,  Journal Article
Song, H; Pavlicek, JW; Cai, F; Bhattacharya, T; Li, H; Iyer, SS; Bar, KJ; Decker, JM; Goonetilleke, N; Liu, MKP; Berg, A; Hora, B; Moody, MA ...
Published in: Retrovirology
October 30, 2012

BACKGROUND: A modest change in HIV-1 fitness can have a significant impact on viral quasispecies evolution and viral pathogenesis, transmission and disease progression. To determine the impact of immune escape mutations selected by cytotoxic T lymphocytes (CTL) on viral fitness in the context of the cognate transmitted/founder (T/F) genome, we developed a new competitive fitness assay using molecular clones of T/F genomes lacking exogenous genetic markers and a highly sensitive and precise parallel allele-specific sequencing (PASS) method. RESULTS: The T/F and mutant viruses were competed in CD4+ T-cell enriched cultures, relative proportions of viruses were assayed after repeated cell-free passage, and fitness costs were estimated by mathematical modeling. Naturally occurring HLA B57-restricted mutations involving the TW10 epitope in Gag and two epitopes in Tat/Rev and Env were assessed independently and together. Compensatory mutations which restored viral replication fitness were also assessed. A principal TW10 escape mutation, T242N, led to a 42% reduction in replication fitness but V247I and G248A mutations in the same epitope restored fitness to wild-type levels. No fitness difference was observed between the T/F and a naturally selected variant carrying the early CTL escape mutation (R355K) in Env and a reversion mutation in the Tat/Rev overlapping region. CONCLUSIONS: These findings reveal a broad spectrum of fitness costs to CTL escape mutations in T/F viral genomes, similar to recent findings reported for neutralizing antibody escape mutations, and highlight the extraordinary plasticity and adaptive potential of the HIV-1 genome. Analysis of T/F genomes and their evolved progeny is a powerful approach for assessing the impact of composite mutational events on viral fitness.

Duke Scholars

Published In

Retrovirology

DOI

EISSN

1742-4690

Publication Date

October 30, 2012

Volume

9

Start / End Page

89

Location

England

Related Subject Headings

  • tat Gene Products, Human Immunodeficiency Virus
  • rev Gene Products, Human Immunodeficiency Virus
  • gag Gene Products, Human Immunodeficiency Virus
  • Virus Replication
  • Virology
  • T-Lymphocytes, Cytotoxic
  • Mutation
  • Molecular Sequence Data
  • Immune Evasion
  • Humans
 

Citation

APA
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ICMJE
MLA
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Song, H., Pavlicek, J. W., Cai, F., Bhattacharya, T., Li, H., Iyer, S. S., … Gao, F. (2012). Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Retrovirology, 9, 89. https://doi.org/10.1186/1742-4690-9-89
Song, Hongshuo, Jeffrey W. Pavlicek, Fangping Cai, Tanmoy Bhattacharya, Hui Li, Shilpa S. Iyer, Katharine J. Bar, et al. “Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome.Retrovirology 9 (October 30, 2012): 89. https://doi.org/10.1186/1742-4690-9-89.
Song H, Pavlicek JW, Cai F, Bhattacharya T, Li H, Iyer SS, et al. Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Retrovirology. 2012 Oct 30;9:89.
Song, Hongshuo, et al. “Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome.Retrovirology, vol. 9, Oct. 2012, p. 89. Pubmed, doi:10.1186/1742-4690-9-89.
Song H, Pavlicek JW, Cai F, Bhattacharya T, Li H, Iyer SS, Bar KJ, Decker JM, Goonetilleke N, Liu MKP, Berg A, Hora B, Drinker MS, Eudailey J, Pickeral J, Moody MA, Ferrari G, McMichael A, Perelson AS, Shaw GM, Hahn BH, Haynes BF, Gao F. Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome. Retrovirology. 2012 Oct 30;9:89.
Journal cover image

Published In

Retrovirology

DOI

EISSN

1742-4690

Publication Date

October 30, 2012

Volume

9

Start / End Page

89

Location

England

Related Subject Headings

  • tat Gene Products, Human Immunodeficiency Virus
  • rev Gene Products, Human Immunodeficiency Virus
  • gag Gene Products, Human Immunodeficiency Virus
  • Virus Replication
  • Virology
  • T-Lymphocytes, Cytotoxic
  • Mutation
  • Molecular Sequence Data
  • Immune Evasion
  • Humans