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Reversion of CTL escape-variant immunodeficiency viruses in vivo

  1. Author:
    Friedrich, T. C.
    Dodds, E. J.
    Yant, L. J.
    Vojnov, L.
    Rudersdorf, R.
    Cullen, C.
    Evans, D. T.
    Desrosiers, R. C.
    Mothe, 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.

  2. Author Address

    Watkins, DI, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53706 USA. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Calif State Univ San Marcos, San Marcos, CA 92096 USA. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. NCI, AIDS Vaccine Program, Frederick, MD 21702 USA. Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA.
    1. Year: 2004
  2. Journal: Nature Medicine
    1. 10
    2. 3
    3. Pages: 275-281
  4. Type of Article: Article
  1. 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

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