摘要
越来越多的证据表明NKG2D,一种自然杀伤细胞(NK)和CD8 + T细胞的活化型受体,对抗HIV的免疫反应有着重要作用。通过识别由细胞应激如病毒感染所诱导的不同配体的能力,NKG2D活化和刺激产生能导致细胞毒性和细胞因子释放的信号。因此,HIV和其他一些病毒已经具有了能抵抗NKG2D依赖的免疫反应的机制。同时,一方面,通过激活DNA损伤反应(DDR)通路,HIV-1 Vpr蛋白使NKG2DLs表达增加,而其他病毒蛋白(Nef 和 Vif)具有降低NKG2DLs表达水平的能力。此外,最近的研究表明,HIV-1感染的CD4 + T细胞可以释放KG2DLs,特别是对于MICA,一种具有使循环淋巴细胞中NKG2D下调的潜力和允许NKG2D介导的免疫反应逃避的现象。事实上,尽管仍存在争议,HIV-1感染患者中NK细胞和CD8 + T细胞都具有较低水平的NKG2D表达。本文综述了在HIV-1对NKG2D/NKG2DLs影响的最新研究进展,并主要关注于病毒诱导可溶性KG2DLs的释放和其对感染的宿主细胞的免疫监视功能。
关键词: MICA
图形摘要
Current Drug Targets
Title:Release of Soluble Ligands for the Activating NKG2D Receptor: One More Immune Evasion Strategy Evolved by HIV-1 ?
Volume: 17 Issue: 1
Author(s): Erica Giuliani, Lia Vassena, Cristina Cerboni and Margherita Doria
Affiliation:
关键词: MICA
摘要: Increasing lines of evidence indicate that NKG2D, an activating receptor of natural killer (NK) and CD8+ T cells, plays an important role in immune responses against HIV-1. Through its ability to recognize a diverse array of ligands (NKG2DLs) induced by cell ‘stress’ such as viral infection, NKG2D delivers activating and co-stimulatory signals resulting in cytotoxicity and release of cytokines. Therefore, HIV-1 and other viruses have evolved clever mechanisms to counteract NKG2D-dependent immune responses. While, on one hand, the HIV-1 Vpr protein up-regulates NKG2DLs expression by activating the DNA damage response (DDR) pathway, other viral proteins (Nef and Vif) have developed the capacity to reduce NKG2DLs expression levels. In addition, recent evidences suggest that HIV-1-infected CD4+ T cells may release NKG2DLs, particularly MICA, in soluble form, a phenomenon that has the potential to down-modulate NKG2D on circulating lymphocytes and allow evasion of NKG2D-mediated immune responses. Indeed, despite controversial, lower NKG2D expression was found on both NK and CD8+ T cells in HIV-1-infected patients. This review discusses recent advances in the understanding of how HIV-1 affects the NKG2D/NKG2DLs system, with a special focus on virus-induced release of soluble NKG2DLs and its functional implications for the immune surveillance of the infected host.
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Cite this article as:
Erica Giuliani, Lia Vassena, Cristina Cerboni and Margherita Doria , Release of Soluble Ligands for the Activating NKG2D Receptor: One More Immune Evasion Strategy Evolved by HIV-1 ?, Current Drug Targets 2016; 17 (1) . https://dx.doi.org/10.2174/1389450116666150630110329
DOI https://dx.doi.org/10.2174/1389450116666150630110329 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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