title: HIV-1 Nef impairs multiple T-cell functions in antigen-specific immune response in mice.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of, Medicine, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Manabu
authors.initials: M
authors.lastname: Ato
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Kaori
authors.initials: K
authors.lastname: Otake
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kaji
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tsunetsugu-Yokota
authors.forename: Mikako
authors.initials: M
authors.lastname: Fujita
authors.forename: Akio
authors.initials: A
authors.lastname: Adachi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takemori
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D015488:HIV Antigens; D054311:nef Gene Products, Human Immunodeficiency Virus