Laboratory of Immunoinfectivology, Children's Hospital Bambino Gesù, 00165 Rome, Italy.
Virology. 2011 Feb 20;410(2):316-26. doi: 10.1016/j.virol.2010.11.018. Epub 2010 Dec 21.
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-γ1, 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.
免疫激活诱导的 CD4(+)T 淋巴细胞表型变化为这些细胞中 HIV-1 的有效复制提供了最佳环境。HIV-1 的致病性 Nef 蛋白调节 T 细胞受体 (TCR) 信号，但这对细胞激活是产生积极还是消极影响仍存在争议。在此，我们研究了感染野生型或 Nef 缺陷型 HIV-1 的原代 CD4(+)T 淋巴细胞对 TCR 刺激的反应。结果表明，在新分离的静止 T 细胞中，Nef 超诱导 NFAT 和 IL-2 的产生，绕过了早期 TCR 效应分子。相反，在亚最佳激活/静止的 T 细胞中，Nef 抑制 PLC-γ1 的早期磷酸化、NFAT 的诱导和 IL-2 的表达。我们的数据表明，Nef 在调节 TCR 信号方面具有双重作用，旨在促进 HIV-1 在静止和代谢活跃的 CD4(+)T 淋巴细胞中的复制和传播。
