1. HIV-1 Nef impairs multiple T-cell functions in antigen-specific immune response in mice.
- Author
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Fujii H, Ato M, Takahashi Y, Otake K, Hashimoto S, Kaji T, Tsunetsugu-Yokota Y, Fujita M, Adachi A, Nakayama T, Taniguchi M, Koyasu S, and Takemori T
- Subjects
- Animals, B-Lymphocytes immunology, Cell Line, Cell Movement genetics, Cell Movement immunology, Cell Proliferation, Gene Expression Regulation immunology, HIV Infections immunology, Humans, Immunologic Memory genetics, Immunologic Memory immunology, Mice, Mice, Inbred BALB C, Mice, SCID, T-Lymphocytes cytology, T-Lymphocytes virology, nef Gene Products, Human Immunodeficiency Virus genetics, Adaptive Immunity immunology, HIV Antigens immunology, HIV-1 immunology, T-Lymphocytes immunology, nef Gene Products, Human Immunodeficiency Virus immunology
- 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. more...
- Published
- 2011
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