HIV-1 Nef impairs multiple T-cell functions in antigen-specific immune response in mice

Hideki Fujii, Manabu Ato, Yoshimasa Takahashi, Kaori Otake, Shu ichi Hashimoto, Tomohiro Kaji, Yasuko Tsunetsugu-yokota, Mikako Fujita, Akio Adachi, Toshinori Nakayama, Masaru Taniguchi, Shigeo Koyasu, Toshitada Takemori

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


The viral protein Nef is a key element for the progression of HIV disease. Previous in vitro studies suggested that Nef expression in T-cell lines enhanced TCR signaling pathways upon stimulation with TCR cross-linking, leading to the proposal that Nef lowers the threshold of T-cell activation, thus increasing susceptibility to viral replication in immune response. Likewise, the in vivo effects of Nef transgenic mouse models supported T-cell hyperresponse by Nef. However, the interpretation is complicated by Nef expression early in the development of T cells in these animal models. Here, we analyzed the consequence of Nef expression in ovalbumin-specific/CD4+ peripheral T cells by using a novel mouse model and demonstrate that Nef inhibits antigen-specific T-cell proliferation and multiple functions required for immune response in vivo, which includes T-cell helper activity for the primary and memory B-cell response. However, Nef does not completely abrogate T-cell activity, as defined by low levels of cytokine production, which may afford the virus a replicative advantage. These results support a model, in which Nef expression does not cause T-cell hyperresponse in immune reaction, but instead reduces the T-cell activity, that may contribute to a low level of virus spread without viral cytopathic effects.

Original languageEnglish
Pages (from-to)433-441
Number of pages9
JournalInternational immunology
Issue number7
Publication statusPublished - 2011 Jul


  • AIDS
  • Acquired immunity
  • Humoral response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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