HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages
HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages
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DOI：
10.1038/nm822
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发表时间：
2003-02-01
期刊：
影响因子：
82.9
通讯作者：
Aldovini, A
中科院分区：
文献类型：
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作者：
Izmailova, E;Bertley, FMN;Aldovini, A
未成熟的树突状细胞是黏膜暴露后第一批被逆转录病毒感染的细胞。我们通过DNA芯片分析和功能分析探讨了人类免疫缺陷病毒-1(HIV-1)及其TAT反式激活剂对这些初级抗原提呈细胞的影响。我们发现，HIV-1感染或TAT表达诱导未成熟的人树突状细胞表达干扰素(IFN)反应基因，而不诱导成熟。在诱导的基因产物中，有一些趋化因子可以招募激活的T细胞和巨噬细胞，而巨噬细胞是病毒的最终靶细胞。猴免疫缺陷病毒(SIV)感染猕猴的淋巴结树突状细胞中单核细胞趋化蛋白2(MCP-2)水平升高，表明体内逆转录病毒感染过程中也有趋化因子的诱导。这些结果表明，HIV-1 TAT重新编程宿主树突状细胞基因表达，以促进HIV-1感染的扩大。
Immature dendritic cells are among the first cells infected by retroviruses after mucosal exposure. We explored the effects of human immunodeficiency virus-1 (HIV-1) and its Tat transactivator on these primary antigen-presenting cells using DNA microarray analysis and functional assays. We found that HIV-1 infection or Tat expression induces interferon (IFN)-responsive gene expression in immature human dendritic cells without inducing maturation. Among the induced gene products are chemokines that recruit activated T cells and macrophages, the ultimate target cells for the virus. Dendritic cells in the lymph nodes of macaques infected with simian immunodeficiency virus (SIV) have elevated levels of monocyte chemoattractant protein 2 (MCP-2), demonstrating that chemokine induction also occurs during retroviral infection in vivo. These results show that HIV-1 Tat reprograms host dendritic cell gene expression to facilitate expansion of HIV-1 infection.