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Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection.

Publication ,  Journal Article
Ganusov, VV; Goonetilleke, N; Liu, MKP; Ferrari, G; Shaw, GM; McMichael, AJ; Borrow, P; Korber, BT; Perelson, AS
Published in: J Virol
October 2011

HIV-1 often evades cytotoxic T cell (CTL) responses by generating variants that are not recognized by CTLs. We used single-genome amplification and sequencing of complete HIV genomes to identify longitudinal changes in the transmitted/founder virus from the establishment of infection to the viral set point at 1 year after the infection. We found that the rate of viral escape from CTL responses in a given patient decreases dramatically from acute infection to the viral set point. Using a novel mathematical model that tracks the dynamics of viral escape at multiple epitopes, we show that a number of factors could potentially contribute to a slower escape in the chronic phase of infection, such as a decreased magnitude of epitope-specific CTL responses, an increased fitness cost of escape mutations, or an increased diversity of the CTL response. In the model, an increase in the number of epitope-specific CTL responses can reduce the rate of viral escape from a given epitope-specific CTL response, particularly if CD8+ T cells compete for killing of infected cells or control virus replication nonlytically. Our mathematical framework of viral escape from multiple CTL responses can be used to predict the breadth and magnitude of HIV-specific CTL responses that need to be induced by vaccination to reduce (or even prevent) viral escape following HIV infection.

Duke Scholars

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

October 2011

Volume

85

Issue

20

Start / End Page

10518 / 10528

Location

United States

Related Subject Headings

  • Virus Replication
  • Virulence
  • Virology
  • T-Lymphocytes, Cytotoxic
  • Immune Evasion
  • Humans
  • HIV-1
  • HIV Infections
  • Epitopes, T-Lymphocyte
  • Cytotoxicity, Immunologic
 

Citation

APA
Chicago
ICMJE
MLA
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Ganusov, V. V., Goonetilleke, N., Liu, M. K. P., Ferrari, G., Shaw, G. M., McMichael, A. J., … Perelson, A. S. (2011). Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection. J Virol, 85(20), 10518–10528. https://doi.org/10.1128/JVI.00655-11
Ganusov, Vitaly V., Nilu Goonetilleke, Michael K. P. Liu, Guido Ferrari, George M. Shaw, Andrew J. McMichael, Persephone Borrow, Bette T. Korber, and Alan S. Perelson. “Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection.J Virol 85, no. 20 (October 2011): 10518–28. https://doi.org/10.1128/JVI.00655-11.
Ganusov VV, Goonetilleke N, Liu MKP, Ferrari G, Shaw GM, McMichael AJ, et al. Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection. J Virol. 2011 Oct;85(20):10518–28.
Ganusov, Vitaly V., et al. “Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection.J Virol, vol. 85, no. 20, Oct. 2011, pp. 10518–28. Pubmed, doi:10.1128/JVI.00655-11.
Ganusov VV, Goonetilleke N, Liu MKP, Ferrari G, Shaw GM, McMichael AJ, Borrow P, Korber BT, Perelson AS. Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection. J Virol. 2011 Oct;85(20):10518–10528.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

October 2011

Volume

85

Issue

20

Start / End Page

10518 / 10528

Location

United States

Related Subject Headings

  • Virus Replication
  • Virulence
  • Virology
  • T-Lymphocytes, Cytotoxic
  • Immune Evasion
  • Humans
  • HIV-1
  • HIV Infections
  • Epitopes, T-Lymphocyte
  • Cytotoxicity, Immunologic