Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus

Persephone Borrow, Hanna Lewicki, Xiping Wei, Marc S. Horwitz, Nancy Peffer, Heather Meyers, Jay A. Nelson, Jean Edouard Gairin, Beatrice H. Hahn, Michael B.A. Oldstone, George M. Shaw

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1017 Scopus citations

Abstract

The HIV-1-specific cytotoxic T lymphocyte (CTL) response is temporally associated with the decline in viremia during primary HIV-1 infection, but definitive evidence that it is of importance in virus containment has been lacking. Here we show that in a patient whose early CTL response was focused on a highly immunodominant epitope in gp160, there was rapid elimination of the transmitted virus strain and selection for a virus population bearing amino acid changes at a single residue within this epitope, which conferred escape from recognition by epitope-specific CTL. The magnitude (> 100-fold), kinetics (30-72 days from onset of symptoms) and genetic pathways of virus escape from CTL pressure were comparable to virus escape from antiretroviral therapy, indicating the biological significance of the CTL response in vivo. One aim of HIV-1 vaccines should thus be to elicit strong CTL responses against multiple codominant viral epitopes.

Original languageEnglish (US)
Pages (from-to)205-211
Number of pages7
JournalNature medicine
Volume3
Issue number2
DOIs
StatePublished - Feb 19 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Borrow, P., Lewicki, H., Wei, X., Horwitz, M. S., Peffer, N., Meyers, H., Nelson, J. A., Gairin, J. E., Hahn, B. H., Oldstone, M. B. A., & Shaw, G. M. (1997). Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nature medicine, 3(2), 205-211. https://doi.org/10.1038/nm0297-205