Plos pathogens：HIV病毒抵抗机体免疫系统新机制

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近日，加拿大一个研究小组在HIV病毒逃避宿主抗病毒免疫应答机制方面取得重要研究进展。他们揭示了HIV病毒是如何利用免疫系统自身"工具"逃避了机体免疫应答并成功入侵宿主的第一道免疫防线。这一突破性发现发表在国际学术期刊plos pathogens上。

这项研究的目的在于明确HIV如何在感染初始阶段成功躲避机体的抗病毒免疫应答，这一阶段也叫做急性感染阶段。急性感染阶段是决定病毒感染复杂性，感染程度和艾滋病进展情况的关键阶段，也是在这一阶段，HIV病毒在宿主细胞内建立了长期的储蓄池，这些储蓄池中的病毒能够避开免疫系统和抗病毒药物的视线。储蓄池的存在艾滋病治疗的一个主要障碍。

在机体第一道免疫防线抗病毒应答过程中，I型干扰素是一类重要蛋白，其在HIV感染早期阶段发挥重要作用。HIV病毒已经具备抑制干扰素应答的机制，但直到现在，人们对于这一过程仍然了解甚少。

干扰素主要由pDC细胞产生。在这项研究中，研究人员发现当pDC遇到HIV感染细胞，感染细胞表面的BST2蛋白能够调节pDC细胞对干扰素的合成过程。研究人员发现BST2能够与pDC细胞表面的ILT7受体结合并将其激活，随后向下传递信号抑制干扰素合成，阻滞pDC细胞发挥免疫防御功能。非常有趣的是，BST2还能在HIV病毒离开感染细胞进行传播之前将病毒困在细胞表面，而HIV病毒则可以使用病毒蛋白Vpu拮抗BST2的抗病毒活性。



这项研究揭示了HIV病毒利用BST2与ILT7之间的调控过程限制机体抗病毒应答的重要机制，这一机制的发现对于了解HIV 病毒如何在体内传播并导致持续性感染具有重要意义。

（生物谷Bioon.com）

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Vpu Exploits the Cross-Talk between BST2 and the ILT7 Receptor to Suppress Anti-HIV-1 Responses by Plasmacytoid Dendritic Cells

Mariana G. Bego, édouard C?té, Nick Aschman, Johanne Mercier, Winfried Weissenhorn, éric A. Cohen

Plasmacytoid dendritic cells (pDCs) constitute a major source of type-I interferon (IFN-I) production during acute HIV infection. Their activation results primarily from TLR7-mediated sensing of HIV-infected cells. However, the interactions between HIV-infected T cells and pDCs that modulate this sensing process remain poorly understood. BST2/Tetherin is a restriction factor that inhibits HIV release by cross-linking virions onto infected cell surface. BST2 was also shown to engage the ILT7 pDC-specific inhibitory receptor and repress TLR7/9-mediated IFN-I production by activated pDCs. Here, we show that Vpu, the HIV-1 antagonist of BST2, suppresses TLR7-mediated IFN-I production by pDC through a mechanism that relies on the interaction of BST2 on HIV-producing cells with ILT7. Even though Vpu downregulates surface BST2 as a mean to counteract the restriction on HIV-1 release, we also find that the viral protein re-locates remaining BST2 molecules outside viral assembly sites where they are free to bind and activate ILT7 upon cell-to-cell contact. This study shows that through a targeted regulation of surface BST2, Vpu promotes HIV-1 release and limits pDC antiviral responses upon sensing of infected cells. This mechanism of innate immune evasion is likely to be important for an efficient early viral dissemination during acute infection.

http://journals.plos.org/plospat ... ournal.ppat.1005024