Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants

Dan H. Barouch*, Jennifer Powers, Diana M. Truitt, Michael G. Kishko, Janelle C. Arthur, Fred W. Peyerl, Marcelo J. Kuroda, Darci A. Gorgone, Michelle A. Lifton, Carol I. Lord, Vanessa M. Hirsch, David C. Montefiore, Angela Carville, Keith G. Mansfield, Kevin J. Kunstman, Steven M. Wolinsky, Norman L. Letvin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)247-252
Number of pages6
JournalNature Immunology
Volume6
Issue number3
DOIs
StatePublished - 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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