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The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection.

Publication ,  Journal Article
Goonetilleke, N; Liu, MKP; Salazar-Gonzalez, JF; Ferrari, G; Giorgi, E; Ganusov, VV; Keele, BF; Learn, GH; Turnbull, EL; Salazar, MG; Moore, S ...
Published in: J Exp Med
June 8, 2009

Identification of the transmitted/founder virus makes possible, for the first time, a genome-wide analysis of host immune responses against the infecting HIV-1 proteome. A complete dissection was made of the primary HIV-1-specific T cell response induced in three acutely infected patients. Cellular assays, together with new algorithms which identify sites of positive selection in the virus genome, showed that primary HIV-1-specific T cells rapidly select escape mutations concurrent with falling virus load in acute infection. Kinetic analysis and mathematical modeling of virus immune escape showed that the contribution of CD8 T cell-mediated killing of productively infected cells was earlier and much greater than previously recognized and that it contributed to the initial decline of plasma virus in acute infection. After virus escape, these first T cell responses often rapidly waned, leaving or being succeeded by T cell responses to epitopes which escaped more slowly or were invariant. These latter responses are likely to be important in maintaining the already established virus set point. In addition to mutations selected by T cells, there were other selected regions that accrued mutations more gradually but were not associated with a T cell response. These included clusters of mutations in envelope that were targeted by NAbs, a few isolated sites that reverted to the consensus sequence, and bystander mutations in linkage with T cell-driven escape.

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Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

June 8, 2009

Volume

206

Issue

6

Start / End Page

1253 / 1272

Location

United States

Related Subject Headings

  • Viremia
  • Viral Proteins
  • T-Lymphocytes
  • Sequence Analysis, Protein
  • Mutation
  • Molecular Sequence Data
  • Models, Theoretical
  • Immunology
  • Immune System
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Goonetilleke, N., Liu, M. K. P., Salazar-Gonzalez, J. F., Ferrari, G., Giorgi, E., Ganusov, V. V., … McMichael, A. J. (2009). The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med, 206(6), 1253–1272. https://doi.org/10.1084/jem.20090365
Goonetilleke, Nilu, Michael K. P. Liu, Jesus F. Salazar-Gonzalez, Guido Ferrari, Elena Giorgi, Vitaly V. Ganusov, Brandon F. Keele, et al. “The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection.J Exp Med 206, no. 6 (June 8, 2009): 1253–72. https://doi.org/10.1084/jem.20090365.
Goonetilleke N, Liu MKP, Salazar-Gonzalez JF, Ferrari G, Giorgi E, Ganusov VV, et al. The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med. 2009 Jun 8;206(6):1253–72.
Goonetilleke, Nilu, et al. “The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection.J Exp Med, vol. 206, no. 6, June 2009, pp. 1253–72. Pubmed, doi:10.1084/jem.20090365.
Goonetilleke N, Liu MKP, Salazar-Gonzalez JF, Ferrari G, Giorgi E, Ganusov VV, Keele BF, Learn GH, Turnbull EL, Salazar MG, Weinhold KJ, Moore S, CHAVI Clinical Core B, Letvin N, Haynes BF, Cohen MS, Hraber P, Bhattacharya T, Borrow P, Perelson AS, Hahn BH, Shaw GM, Korber BT, McMichael AJ. The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med. 2009 Jun 8;206(6):1253–1272.

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

June 8, 2009

Volume

206

Issue

6

Start / End Page

1253 / 1272

Location

United States

Related Subject Headings

  • Viremia
  • Viral Proteins
  • T-Lymphocytes
  • Sequence Analysis, Protein
  • Mutation
  • Molecular Sequence Data
  • Models, Theoretical
  • Immunology
  • Immune System
  • Humans