Infection of human immunodeficiency virus and intracellular viral Tat protein exert a pro-survival effect in a human microglial cell line.
Infection of human immunodeficiency virus and intracellular viral Tat protein exert a pro-survival effect in a human microglial cell line.
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DOI：
10.1016/j.jmb.2006.11.011
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发表时间：
2007-02-09
影响因子：
5.6
通讯作者：
Kim B
中科院分区：
文献类型：
--
作者：
Chugh P;Fan S;Planelles V;Maggirwar SB;Dewhurst S;Kim B
人类免疫缺陷病毒 1 型 (HIV-1) 与 CD4+ T 淋巴细胞的相互作用已得到充分研究，通常会导致病毒诱导的细胞溶解。相比之下，人们对 HIV-1 和小胶质细胞之间的相互作用知之甚少。最近的研究结果表明，与直觉相反，HIV-1 感染可能会延长小胶质细胞的寿命。我们开发了一种新型细胞系模型系统来证实并从机制上研究这种现象。我们发现用 HIV-1 载体转导人小胶质细胞系可在细胞凋亡挑战后产生强大的细胞保护作用。这种效应通过单一病毒编码蛋白 Tat 的异位表达而重现。随后的研究表明，细胞内 Tat 的促生存作用可归因于小胶质细胞系中 PI-3 激酶 (PI3K)/Akt 通路的激活。此外，我们发现 Tat 的表达导致 PTEN（PI-3-K 通路的负调节因子）的表达减少。与此一致的是，观察到 p53 活性降低和 E2F 活性增加。基于这些发现，提出了细胞内 Tat 和 HIV-1 感染在小胶质细胞的细胞保护事件期间参与的可能调节回路模型。我们认为，Tat 的表达可能使 HIV-1 感染的小胶质细胞在整个感染过程中存活，从而导致中枢神经系统中持续的 HIV-1 产生和感染。
The interaction of human immunodeficiency virus type 1 (HIV-1) with CD4+ T lymphocytes is well studied and typically results in virally induced cytolysis. In contrast, relatively little is known concerning the interplay between HIV-1 and microglia. Recent findings suggest that, counter-intuitively, HIV-1 infection may extend the lifespan of microglia. We developed a novel cell line model system to confirm and mechanistically study this phenomenon. We found that transduction of a human microglial cell line with an HIV-1 vector results in a powerful cytoprotective effect following apoptotic challenge. This effect was reproduced by ectopic expression of a single virus-encoded protein, Tat. Subsequent studies showed that the pro-survival effects of intracellular Tat could be attributed to activation of the PI-3-kinase (PI3K)/Akt pathway in the microglial cell line. Furthermore, we found that expression of Tat led to decreased expression of PTEN, a negative regulator of the PI-3-K pathway. Consistent with this, decreased p53 activity and increased E2F activity were observed. Based on these findings, a model of possible regulatory circuits that intracellular Tat and HIV-1 infection engage during the cytoprotective event in microglia has been suggested. We propose that the expression of Tat may enable HIV-1 infected microglia to survive throughout the course of infection, leading to persistent HIV-1 production and infection in the central nervous system.
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影响因子：
4.4
作者：
Boehme, SA;Lio, FM;Conlon, PJ
通讯作者：
Conlon, PJ
DOI：
10.1152/ajpheart.00453.2004
发表时间：
2005-01-01
影响因子：
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作者：
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影响因子：
4.8
作者：
Fortin, JF;Barat, C;Tremblay, MJ
通讯作者：
Tremblay, MJ