Simian-Human Immunodeficiency Virus Escape from Cytotoxic T-Lymphocyte Recognition at a Structurally Constrained Epitope

Fred W. Peyerl, Dan H. Barouch, Wendy W. Yeh, Heidi S. Bazick, Jennifer Kunstman, Kevin J. Kunstman, Steven M. Wolinsky, Norman L. Letvin

Research output: Contribution to journalArticle

Abstract

Virus-specific cytotoxic T lymphocytes (CTL) exert intense selection pressure on replicating simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) in infected individuals. The immunodominant Mamu-A*01-restricted Gag p11C, C-M epitope is highly conserved among all sequenced isolates of SIV and therefore likely is structurally constrained. The strategies used by virus isolates to mutate away from an immunodominant epitope-specific CTL response are not well defined. Here we demonstrate that the emergence of a position 2 p11C, C-M epitope substitution (T47I) in a simian-human immunodeficiency virus (SHIV) strain 89.6P-infected Mamu-A*01+ monkey is temporally correlated with the emergence of a flanking isoleucine-to-valine substitution at position 71 (I71V) of the capsid protein. An analysis of the SIV and HIV-2 sequences from the Los Alamos HIV Sequence Database revealed a significant association between any position 2 p11C, C-M epitope mutation and the I71V mutation. The T47I mutation alone is associated with significant decreases in viral protein expression, infectivity, and replication, and these deficiencies are restored to wild-type levels with the introduction of the flanking I71V mutation. Together, these data suggest that a compensatory mutation is selected for in SHIV strain 89.6P to facilitate the escape of that virus from CTL recognition of the dominant p11C, C-M epitope.

Original languageEnglish (US)
Pages (from-to)12572-12578
Number of pages7
JournalJournal of virology
Volume77
Issue number23
DOIs
StatePublished - Dec 1 2003

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Peyerl, F. W., Barouch, D. H., Yeh, W. W., Bazick, H. S., Kunstman, J., Kunstman, K. J., Wolinsky, S. M., & Letvin, N. L. (2003). Simian-Human Immunodeficiency Virus Escape from Cytotoxic T-Lymphocyte Recognition at a Structurally Constrained Epitope. Journal of virology, 77(23), 12572-12578. https://doi.org/10.1128/JVI.77.23.12572-12578.2003