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 C. 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 I. Watkins*

*Corresponding author for this work

Research output: Contribution to journalArticle

316 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Friedrich, T. C., Dodds, E. J., Yant, L. J., Vojnov, L., Rudersdorf, R., Cullen, C., Evans, D. T., Desrosiers, R. C., Mothé, B. R., Sidney, J., Sette, A., Kunstman, K., Wolinsky, S., Piatak, M., Lifson, J., Hughes, A. L., Wilson, N., O'Connor, D. H., & Watkins, D. I. (2004). Reversion of CTL escape-variant immunodeficiency viruses in vivo. Nature Medicine, 10(3), 275-281. https://doi.org/10.1038/nm998