CTL escape and increased viremia irrespective of HIV-specific CD4+ T-helper responses in two HIV-infected individuals

Mark J Geels*, Christine A Jansen, Elly Baan, Iris M De Cuyper, Gijs J M van Schijndel, Hanneke Schuitemaker, Jaap Goudsmit, Georgios Pollakis, Frank Miedema, William A Paxton, Debbie van Baarle

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)

Abstract

We investigated whether development of mutations leads to loss of CD8 T-cell recognition in HIV-1 infection and is possibly linked to alterations in HIV-1-specific CD4(+) T-cell responses in 2 HIV-infected individuals. In patient, H434 full genome sequencing of HIV-1 biological clones at early and late time points during disease progression showed development of fixed mutations in 16 predicted HIV-specific CTL epitopes. Loss of T-cell recognition and reactivity against wild-type and mutant epitopes was observed primarily for the HLA-B27-restricted KK10 epitope and HLA-A2-restricted SL9 epitope. Similarly, in patient H671, decreasing numbers of HLA-A3-restricted CD8(+) T cells specific for the wild-type RK9 epitope was observed after CTL escape. Only in patient H434 loss of CTL responses was paralleled by a decrease in HIV-specific IL-2(+) CD4(+) T-helper responses. This suggests that loss of T-cell reactivity may not be directly linked to HIV-specific CD4(+) T-cell responses but that increased viremia after CTL escape may influence CD4(+) T-helper responses.

Original languageEnglish
Pages (from-to)209-219
Number of pages11
JournalVirology
Volume345
Issue number1
DOIs
Publication statusPublished - 5-Feb-2006
Externally publishedYes

Keywords

  • Epitopes, T-Lymphocyte/genetics
  • Genome, Viral
  • HIV Infections/immunology
  • HIV-1/genetics
  • Humans
  • Lymphocyte Count
  • Mutation
  • T-Lymphocytes, Cytotoxic/immunology
  • T-Lymphocytes, Helper-Inducer/immunology
  • Viremia

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