Selective pressure exerted by immunodominant HIV-1-specific cytotoxic T lymphocyte responses during primary infection drives genetic variation restricted to the cognate epitope

Hugo Soudeyns, Stefania Paolucci, Colombe Chappey, Mary Beth Daucher, Cecilia Graziosi, Mauro Vaccarezza, Oren J. Cohen, Anthony S. Fauci, Giuseppe Pantaleo

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

HIV-specific cytotoxic T lymphocytes (CTL) play a central role in the control of HIV-1 replication during primary infection. It has been hypothesized that the appearance of CTL escape mutants represents an important mechanism by which HIV-1 escapes the host cell-mediated immune response. However, evidences for a direct relationship between CTL responses and emergence of CTL escape mutants are still limited. Here we report detailed longitudinal analysis of DNA sequence variation performed over the entire HIV-1 envelope in two subjects during primary HIV infection. Estimates of the frequencies of synonymous (dS) and non-synonymous (dN) nucleotide substitutions were used to identify regions of the HIV-1 envelope which were subjected to significant levels of selective pressure. These regions were shown to comprise defined epitopes recognized by CTL. Furthermore, dN mutation fixed within these epitopes effectively abolished recognition by the host CTL response. These results provide compelling evidence that the CTL epitope mutations directly resulted from the selective pressure exerted by the virus-specific cytotoxic response.

Original languageEnglish
Pages (from-to)3629-3635
Number of pages7
JournalEuropean Journal of Immunology
Volume29
Issue number11
DOIs
Publication statusPublished - 1999

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Cytotoxic T-Lymphocytes
HIV-1
Epitopes
Infection
Mutation
T-Lymphocyte Epitopes
DNA Sequence Analysis
HIV Infections
Nucleotides
HIV
Viruses

Keywords

  • Cytotoxic T lymphocyte
  • HIV-1
  • Viral escape mutation

ASJC Scopus subject areas

  • Immunology

Cite this

Selective pressure exerted by immunodominant HIV-1-specific cytotoxic T lymphocyte responses during primary infection drives genetic variation restricted to the cognate epitope. / Soudeyns, Hugo; Paolucci, Stefania; Chappey, Colombe; Daucher, Mary Beth; Graziosi, Cecilia; Vaccarezza, Mauro; Cohen, Oren J.; Fauci, Anthony S.; Pantaleo, Giuseppe.

In: European Journal of Immunology, Vol. 29, No. 11, 1999, p. 3629-3635.

Research output: Contribution to journalArticle

Soudeyns, Hugo ; Paolucci, Stefania ; Chappey, Colombe ; Daucher, Mary Beth ; Graziosi, Cecilia ; Vaccarezza, Mauro ; Cohen, Oren J. ; Fauci, Anthony S. ; Pantaleo, Giuseppe. / Selective pressure exerted by immunodominant HIV-1-specific cytotoxic T lymphocyte responses during primary infection drives genetic variation restricted to the cognate epitope. In: European Journal of Immunology. 1999 ; Vol. 29, No. 11. pp. 3629-3635.
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AU - Daucher, Mary Beth

AU - Graziosi, Cecilia

AU - Vaccarezza, Mauro

AU - Cohen, Oren J.

AU - Fauci, Anthony S.

AU - Pantaleo, Giuseppe

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