Reversion of CTL escape-variant immunodeficiency viruses in vivo.

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.

• Authors: 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
• Journal: Nature medicine (Nat Med) Vol. 10 Issue 3 Pg. 275-81 (Mar 2004) ISSN: 1078-8956 [Print] United States
• PMID: 14966520 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• AIDS Vaccines
• HLA Antigens
• Immunodominant Epitopes

Topics

• AIDS Vaccines
• Amino Acid Sequence
• Animals
• Evolution, Molecular
• Genes, MHC Class I
• HLA Antigens (metabolism)
• Humans
• Immunodominant Epitopes (genetics, immunology)
• Macaca mulatta
• Molecular Sequence Data
• Mutation
• Sequence Alignment
• Simian Acquired Immunodeficiency Syndrome (immunology, virology)
• Simian Immunodeficiency Virus (genetics, immunology, pathogenicity, physiology)
• T-Lymphocytes, Cytotoxic (immunology, metabolism)
• Virus Replication (physiology)