Different in vivo effects of HIV-1 immunodominant epitope-specific cytotoxic T lymphocytes on selection of escape mutant viruses

Hirokazu Koizumi, Masao Hashimoto, Mamoru Fujiwara, Hayato Murakoshi, Takayuki Chikata, Mohamed Ali Borghan, Atsuko Hachiya, Yuka Kawashima, Hiroshi Takata, Takamasa Ueno, Shinichi Oka, Masafumi Takiguchi

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

HIV-1 escape mutants are well known to be selected by immune pressure via HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies. The ability of the CTLs to suppress HIV-1 replication is assumed to be associated with the selection of escape mutants from the CTLs. Therefore, we first investigated the correlation between the ability of HLA-A*1101-restricted CTLs recognizing immunodominant epitopes in vitro and the selection of escape mutants. The result showed that there was no correlation between the ability of these CTLs to suppress HIV-1 replication in vitro and the appearance of escape mutants. The CTLs that had a strong ability to suppress HIV-1 replication in vitro but failed to select escape mutants expressed a higher level of PD-1 in vivo, whereas those that had a strong ability to suppress HIV-1 replication in vitro and selected escape mutants expressed a low level of PD-1. Ex vivo analysis of these CTLs revealed that the latter CTLs had a significantly stronger ability to recognize the epitope than the former ones. These results suggest that escape mutations are selected by HIV-1-specific CTLs that have a stronger ability to recognize HIV-1 in vivo but not in vitro.

Original languageEnglish (US)
Pages (from-to)5508-5519
Number of pages12
JournalJournal of virology
Volume84
Issue number11
DOIs
StatePublished - Jun 2010
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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