Abstract
Viral escape from cytotoxic T lymphocytes (CTLs) can undermine immune control of human immunodeficiency virus 1. It is therefore important to assess the stability of viral mutations in CTL epitopes after transmission to naive hosts. Here we demonstrate the persistence of mutations in a dominant CTL epitope after transmission of simian immunodeficiency virus variants to major histocompatibility complex–matched rhesus monkeys. Transient reversions to wild-type sequences occurred and elicited CTLs specific for the wild-type epitope, resulting in immunological pressure that rapidly reselected the mutant viruses. These data suggest that mutations in dominant human immunodeficiency virus 1 CTL epitopes may accumulate in human populations with limited major histocompatibility complex heterogeneity by a mechanism involving dynamic CTL control of transiently reverted wild-type virus.
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Acknowledgements
We thank S. Sumida, J. Schmitz, S. Santra, and K. Reimann for advice, assistance and reagents. Peptides were obtained from the National Institutes of Health AIDS Research and Reference Reagent Program. Supported by US National Institutes of Health (AI-20729 to N.L.L.; AI-58727 and AI-51223 to D.H.B.; and P51 RR-00168 to the New England Primate Research Center).
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Barouch, D., Powers, J., Truitt, D. et al. Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants. Nat Immunol 6, 247–252 (2005). https://doi.org/10.1038/ni1167
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DOI: https://doi.org/10.1038/ni1167
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