Reversion of CTL escape-variant immunodeficiency viruses in vivo

Thomas C. Friedrich, Elizabeth J. Dodds, Levi J. Yant, Lara Vojnov, Richard Rudersdorf, Candice Cullen, David T. Evans, Ronald Charles Desrosiers, Bianca R. Mothé, John Sidney, Alessandro Sette, Kevin Kunstman, Steven Wolinsky, Michael Piatak, Jeffrey Lifson, Austin L. Hughes, Nancy Wilson, David H. O'Connor, David Watkins

Research output: Contribution to journalArticle

313 Citations (Scopus)

Abstract

Engendering cytotoxic T-lymphocyte (CTL) responses is likely to be an important goal of HIV vaccines. However, CTLs select for viral variants that escape immune detection. Maintenance of such escape variants in human populations could pose an obstacle to HIV vaccine development. We first observed that escape mutations in a heterogeneous simian immunodeficiency virus (SIV) isolate were lost upon passage to new animals. We therefore infected macaques with a cloned SIV bearing escape mutations in three immunodominant CTL epitopes, and followed viral evolution after infection. Here we show that each mutant epitope sequence continued to evolve in vivo, often re-establishing the original, CTL-susceptible sequence. We conclude that escape from CTL responses may exact a cost to viral fitness. In the absence of selective pressure upon transmission to new hosts, these original escape mutations can be lost. This suggests that some HIV CTL epitopes will be maintained in human populations.

Original languageEnglish
Pages (from-to)275-281
Number of pages7
JournalNature Medicine
Volume10
Issue number3
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

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T-cells
Cytotoxic T-Lymphocytes
Viruses
AIDS Vaccines
T-Lymphocyte Epitopes
Bearings (structural)
Simian Immunodeficiency Virus
Mutation
Epitopes
Animals
Macaca
Population
Maintenance
HIV
Costs
Costs and Cost Analysis
Infection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Friedrich, T. C., Dodds, E. J., Yant, L. J., Vojnov, L., Rudersdorf, R., Cullen, C., ... Watkins, D. (2004). Reversion of CTL escape-variant immunodeficiency viruses in vivo. Nature Medicine, 10(3), 275-281. https://doi.org/10.1038/nm998

Reversion of CTL escape-variant immunodeficiency viruses in vivo. / Friedrich, Thomas C.; Dodds, Elizabeth J.; Yant, Levi J.; Vojnov, Lara; Rudersdorf, Richard; Cullen, Candice; Evans, David T.; Desrosiers, Ronald Charles; Mothé, Bianca R.; Sidney, John; Sette, Alessandro; Kunstman, Kevin; Wolinsky, Steven; Piatak, Michael; Lifson, Jeffrey; Hughes, Austin L.; Wilson, Nancy; O'Connor, David H.; Watkins, David.

In: Nature Medicine, Vol. 10, No. 3, 01.03.2004, p. 275-281.

Research output: Contribution to journalArticle

Friedrich, TC, Dodds, EJ, Yant, LJ, Vojnov, L, Rudersdorf, R, Cullen, C, Evans, DT, Desrosiers, RC, Mothé, BR, Sidney, J, Sette, A, Kunstman, K, Wolinsky, S, Piatak, M, Lifson, J, Hughes, AL, Wilson, N, O'Connor, DH & Watkins, D 2004, 'Reversion of CTL escape-variant immunodeficiency viruses in vivo', Nature Medicine, vol. 10, no. 3, pp. 275-281. https://doi.org/10.1038/nm998
Friedrich TC, Dodds EJ, Yant LJ, Vojnov L, Rudersdorf R, Cullen C et al. Reversion of CTL escape-variant immunodeficiency viruses in vivo. Nature Medicine. 2004 Mar 1;10(3):275-281. https://doi.org/10.1038/nm998
Friedrich, Thomas C. ; Dodds, Elizabeth J. ; Yant, Levi J. ; Vojnov, Lara ; Rudersdorf, Richard ; Cullen, Candice ; Evans, David T. ; Desrosiers, Ronald Charles ; Mothé, Bianca R. ; Sidney, John ; Sette, Alessandro ; Kunstman, Kevin ; Wolinsky, Steven ; Piatak, Michael ; Lifson, Jeffrey ; Hughes, Austin L. ; Wilson, Nancy ; O'Connor, David H. ; Watkins, David. / Reversion of CTL escape-variant immunodeficiency viruses in vivo. In: Nature Medicine. 2004 ; Vol. 10, No. 3. pp. 275-281.
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