The HIV-1 Nef protein has a dual role in T cell receptor signaling in infected CD4+ T lymphocytes
The HIV-1 Nef protein has a dual role in T cell receptor signaling in infected CD4+ T lymphocytes
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DOI:
10.1016/j.virol.2010.11.018
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发表时间:
2011-02-20
期刊:
影响因子:
3.7
通讯作者:
Doria, Margherita
中科院分区:
文献类型:
--
作者:
Neri, Francesca;Giolo, Giorgia;Doria, Margherita
The phenotypic changes that are induced by immune activation in CD4(+) T lymphocytes provide an optimal environment for efficient HIV-1 replication in these cells. The pathogenic Nef protein of HIV-1 modulates the T cell receptor (TCR) signaling, but whether this has a positive or negative effect on cellular activation is a matter of debate. Here we have investigated the response to TCR stimulation of primary CD4(+) T lymphocytes infected with wt or Nef-deficient HIV-1. Results show that, in freshly isolated quiescent T cells, Nef superinduces NFAT and IL-2 production bypassing early TCR effector molecules. Conversely, the early phosphorylation of PLC-gamma 1, the induction of NFAT, and the expression of IL-2 are impaired by Nef in sub-optimally activated/resting T cells. Our data indicate that Nef has a dual role in the modulation of TCR signaling aimed at favoring HIV-1 replication and spread in both quiescent and metabolically active CD4(+) T lymphocytes. (C) 2010 Elsevier Inc. All rights reserved.