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Acute-phase CD8 T cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus.

Publication ,  Journal Article
Harris, M; Burns, CM; Becker, EA; Braasch, AT; Gostick, E; Johnson, RC; Broman, KW; Price, DA; Friedrich, TC; O'Connor, SL
Published in: J Virol
August 2013

The overall CD8 T cell response to human/simian immunodeficiency virus (HIV/SIV) targets a collection of discrete epitope specificities. Some of these epitope-specific CD8 T cells emerge in the weeks and months following infection and rapidly select for sequence variants, whereas other CD8 T cell responses develop during the chronic infection phase and rarely select for sequence variants. In this study, we tested the hypothesis that acute-phase CD8 T cell responses that do not rapidly select for escape variants are unable to control viral replication in vivo as well as those that do rapidly select for escape variants. We created a derivative of live attenuated SIV (SIVmac239Δnef) in which we ablated five epitopes that elicit early CD8 T cell responses and rapidly accumulate sequence variants in SIVmac239-infected Mauritian cynomolgus macaques (MCMs) that are homozygous for the M3 major histocompatibility complex (MHC) haplotype. This live attenuated SIV variant was called m3KOΔnef. Viremia was significantly higher in M3 homozygous MCMs infected with m3KOΔnef than in either MHC-mismatched MCMs infected with m3KOΔnef or MCMs infected with SIVmac239Δnef. Three CD8 T cell responses, including two that do not rapidly select for escape variants, predominated during early m3KOΔnef infection in the M3 homozygous MCMs, but these animals were unable to control viral replication. These results provide evidence that acute-phase CD8 T cell responses that have the potential to rapidly select for escape variants in the early phase of infection are needed to establish viral control in vivo.

Duke Scholars

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

August 2013

Volume

87

Issue

16

Start / End Page

9353 / 9364

Location

United States

Related Subject Headings

  • Virology
  • Viremia
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Selection, Genetic
  • Macaca
  • Immune Evasion
  • Genetic Variation
  • CD8-Positive T-Lymphocytes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Harris, M., Burns, C. M., Becker, E. A., Braasch, A. T., Gostick, E., Johnson, R. C., … O’Connor, S. L. (2013). Acute-phase CD8 T cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus. J Virol, 87(16), 9353–9364. https://doi.org/10.1128/JVI.00909-13
Harris, Max, Charles M. Burns, Ericka A. Becker, Andrew T. Braasch, Emma Gostick, Randall C. Johnson, Karl W. Broman, David A. Price, Thomas C. Friedrich, and Shelby L. O’Connor. “Acute-phase CD8 T cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus.J Virol 87, no. 16 (August 2013): 9353–64. https://doi.org/10.1128/JVI.00909-13.
Harris M, Burns CM, Becker EA, Braasch AT, Gostick E, Johnson RC, et al. Acute-phase CD8 T cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus. J Virol. 2013 Aug;87(16):9353–64.
Harris, Max, et al. “Acute-phase CD8 T cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus.J Virol, vol. 87, no. 16, Aug. 2013, pp. 9353–64. Pubmed, doi:10.1128/JVI.00909-13.
Harris M, Burns CM, Becker EA, Braasch AT, Gostick E, Johnson RC, Broman KW, Price DA, Friedrich TC, O’Connor SL. Acute-phase CD8 T cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus. J Virol. 2013 Aug;87(16):9353–9364.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

August 2013

Volume

87

Issue

16

Start / End Page

9353 / 9364

Location

United States

Related Subject Headings

  • Virology
  • Viremia
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Selection, Genetic
  • Macaca
  • Immune Evasion
  • Genetic Variation
  • CD8-Positive T-Lymphocytes