Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection

David H. O’connor, Todd M. Allen, Thorsten U. Vogel, Peicheng Jing, Ivna P. DeSouza, Elizabeth Dodds, Edward J. Dunphy, Cheri Melsaether, Bianca Mothé, Hiroshi Yamamoto, Helen Horton, Nancy Wilson, Austin L. Hughes, David I. Watkins

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318 Scopus citations

Abstract

Cytotoxic T-lymphocyte (CTL) responses peak coincident with the decline in acute HIV viremia. Despite two reports of CTL-resistant HIV variants emerging during acute infection, the contribution of acute CTL escape to HIV pathogenesis remains unclear. Difficulties inherent in studying acute HIV infection can be overcome by modeling virus-host interactions in SIV-infected rhesus macaques. We sequenced 21 complete simian immunodeficiency virus (SIV)mac239 genomes at four weeks post-infection to determine the extent of acute CTL escape. Here we show that viruses from 19 of 21 macaques escaped from CTLs during acute infection and that these escapeselecting CTLs were responsive to lower concentrations of peptide than other SIV-specific CTLs. Interestingly, CTLs that require low peptide concentrations for stimulation (high 'functional avidity') are particularly effective at controlling other viral infections. Our results suggest that acute viral escape from CTLs is a hallmark of SIV infection and that CTLs with high functional avidity can rapidly select for escape variants.

Original languageEnglish (US)
Pages (from-to)493-499
Number of pages7
JournalNature medicine
Volume8
Issue number5
DOIs
StatePublished - Jan 1 2002

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

O’connor, D. H., Allen, T. M., Vogel, T. U., Jing, P., DeSouza, I. P., Dodds, E., Dunphy, E. J., Melsaether, C., Mothé, B., Yamamoto, H., Horton, H., Wilson, N., Hughes, A. L., & Watkins, D. I. (2002). Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection. Nature medicine, 8(5), 493-499. https://doi.org/10.1038/nm0502-493