Izmailova Elena, Bertley Frederic M N, Huang Qian, Makori Norbert, Miller Christopher J, Young Richard A, Aldovini Anna
Department of Medicine, Children's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
Nat Med. 2003 Feb;9(2):191-7. doi: 10.1038/nm822. Epub 2003 Jan 21.
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.
未成熟的树突状细胞是黏膜暴露后最早被逆转录病毒感染的细胞之一。我们使用DNA微阵列分析和功能测定法，探究了人类免疫缺陷病毒1型（HIV-1）及其反式激活因子Tat对这些主要抗原呈递细胞的影响。我们发现，HIV-1感染或Tat表达可在未成熟的人类树突状细胞中诱导干扰素（IFN）反应性基因表达，而不会诱导其成熟。诱导的基因产物中包括趋化因子，这些趋化因子可募集活化的T细胞和巨噬细胞，而后者是该病毒的最终靶细胞。感染猿猴免疫缺陷病毒（SIV）的猕猴淋巴结中的树突状细胞，其单核细胞趋化蛋白2（MCP-2）水平升高，这表明在体内逆转录病毒感染过程中也会发生趋化因子诱导。这些结果表明，HIV-1 Tat可对宿主树突状细胞基因表达进行重编程，以促进HIV-1感染的扩散。
