Extraepitopic Compensatory Substitutions Partially Restore Fitness to Simian Immunodeficiency Virus Variants that Escape from an Immunodominant Cytotoxic-T-Lymphocyte Response

Thomas C. Friedrich, Christopher A. Frye, Levi J. Yant, David H. O'Connor, Nancy A. Kriewaldt, Meghan Benson, Lara Vojnov, Elizabeth J. Dodds, Candice Cullen, Richard Rudersdorf, Austin L. Hughes, Nancy Wilson, David I. Watkins

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Selection for escape mutant immunodeficiency viruses by cytotoxic T lymphocytes (CTL) has been well characterized and may be associated with disease progression. CTL epitopes accrue escape mutations at different rates in vivo. Interestingly, certain high-frequency CTL do not select for escape until the chronic phase of infection. Here we show that mutations conferring escape from immunodominant CTL directed against an epitope in the viral Gag protein are strongly associated with extraepitopic mutations in gag in vivo. The extraepitopic mutations partially restore in vitro replicative fitness of viruses bearing the escape mutations. Constraints on epitope sequences may therefore play a role in determining the rate of escape from CTL responses in vivo.

Original languageEnglish (US)
Pages (from-to)2581-2585
Number of pages5
JournalJournal of virology
Volume78
Issue number5
DOIs
StatePublished - Mar 2004
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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