HIV Type 1 Nef Is Released from Infected Cells in CD45+ Microvesicles and Is Present in the Plasma of HIV-Infected Individuals
HIV Type 1 Nef Is Released from Infected Cells in CD45+ Microvesicles and Is Present in the Plasma of HIV-Infected Individuals
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DOI：
10.1089/aid.2009.0170
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发表时间：
2011-02-01
影响因子：
1.5
通讯作者：
Powell, M. D.
中科院分区：
文献类型：
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作者：
Raymond, A. D.;Campbell-Sims, T. C.;Powell, M. D.
HIV-1 Nef已被证明是病毒持久性、传染性和加速人类疾病发病机制（AIDS）的组成部分。Nef也在HIV感染者的血浆中被检测到，并从感染的细胞中释放出来。Nef从受感染细胞中释放的形式尚不清楚。然而，Nef是一种豆蔻酰化的蛋白质，并已被证明与细胞内囊泡运输网络相互作用。在这里，我们表明Nef是在含有CD 45的微泡中释放的。这种微泡Nef（mvNef）在HIV感染个体的血浆中以相对高的浓度（10 ng/ml）被检测到。它也存在于感染HIVMN的Jurkat细胞的组织培养上清液中。有趣的是，HIV+患者的血浆mvNef水平与病毒载量或CD 4计数没有显着相关性。尽管使用抗逆转录病毒治疗，HIV感染者血浆中的微泡Nef水平仍然存在，即使在病毒载量检测不到的个体中也是如此。使用细胞系，我们发现Nef微泡诱导Jurkat T淋巴细胞凋亡，但对U937单核细胞系没有观察到影响。鉴于大量的mvNef存在于HIV感染者的血浆中，mvNef对T细胞的凋亡作用，以及在体外观察到的细胞外可溶性Nef的功能，似乎体内mvNef可能在AIDS的发病机制中发挥重要作用。
HIV-1 Nef has been demonstrated to be integral for viral persistence, infectivity, and the acceleration of disease pathogenesis (AIDS) in humans. Nef has also been detected in the plasma of HIV-infected individuals and is released from infected cells. The form in which Nef is released from infected cells is unknown. However, Nef is a myristoylated protein and has been shown to interact with the intracellular vesicular trafficking network. Here we show that Nef is released in CD45-containing microvesicles. This microvesicular Nef (mvNef) is detected in the plasma of HIV-infected individuals at relatively high concentrations (10 ng/ml). It is also present in tissue culture supernatants of Jurkat cells infected with HIVMN. Interestingly, plasma mvNef levels in HIV+ patients did not significantly correlate with viral load or CD4 count. Microvesicular Nef levels persisted in the plasma of HIV-infected individuals despite the use of antiretroviral therapy, even in individuals with undetectable viral loads. Using cell lines, we found Nef microvesicles induce apoptosis in Jurkat T-lymphocytes but had no observed effect on the U937 monocytic cell line. Given the large amount of mvNef present in the plasma of HIV-infected individuals, the apoptotic effect of mvNef on T cells, and the observed functions of extracellular soluble Nef in vitro, it seems likely that in vivo mvNef may play a significant role in the pathogenesis of AIDS.