HSV1 MicroRNA Modulation of GPI Anchoring and Downstream Immune Evasion.
HSV1 MicroRNA Modulation of GPI Anchoring and Downstream Immune Evasion.
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DOI：
10.1016/j.celrep.2016.09.077
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发表时间：
2016-10-18
期刊：
影响因子：
8.8
通讯作者：
Mandelboim O
中科院分区：
文献类型：
--
作者：
Enk J;Levi A;Weisblum Y;Yamin R;Charpak-Amikam Y;Wolf DG;Mandelboim O
单纯疱疹病毒1型（HSV1）是一种普遍存在的人类病原体，利用可变的机制来逃避免疫监视。糖基磷脂酰肌醇（GPI）锚定途径是一个多步骤的过程，其中无数不同的蛋白质共价连接到GPI部分，呈现在细胞表面上。在不同的GPI锚定蛋白中，有许多具有免疫学重要性。我们提出的证据表明，HSV 1编码的miR H8直接靶向PIGT，蛋白质复合物的成员，共价连接蛋白质GPI在GPI锚定的最后一步。这导致几种不同的免疫相关的GPI锚定蛋白的膜下调，包括天然生物素活化受体的配体和突出的病毒限制因子tetherin。因此，我们认为，通过利用HSV1编码的数十种miRNA中的一种，病毒可以在几个关键点上抵消宿主的免疫反应。HSV 1 miR H8靶向GPI锚定途径的PIGT抗病毒蛋白质系链蛋白的表达减少，病毒扩散增强GPI锚定的活化NK细胞配体的表达减少NK细胞的识别和消除减少单纯疱疹病毒1是一种普遍存在的人类病原体，是多种疾病的原因。Enk等人发现HSV1编码的miR H8靶向GPI锚定途径，减少几种免疫调节蛋白的表达，从而增强病毒传播并使自然杀伤细胞的消除得以逃避。
Herpes simplex virus 1 (HSV1) is a ubiquitous human pathogen that utilizes variable mechanisms to evade immune surveillance. The glycosylphosphatidylinositol (GPI) anchoring pathway is a multistep process in which a myriad of different proteins are covalently attached to a GPI moiety to be presented on the cell surface. Among the different GPI-anchored proteins there are many with immunological importance. We present evidence that the HSV1-encoded miR H8 directly targets PIGT, a member of the protein complex that covalently attaches proteins to GPI in the final step of GPI anchoring. This results in a membrane down-modulation of several different immune-related, GPI-anchored proteins, including ligands for natural killer-activating receptors and the prominent viral restriction factor tetherin. Thus, we suggest that by utilizing just one of dozens of miRNAs encoded by HSV1, the virus can counteract the host immune response at several key points. HSV1 miR H8 targets PIGT of the GPI anchoring pathway Expression of the anti-viral protein tetherin is reduced and viral spread enhanced Expression of GPI-anchored activating NK cell ligands is reduced Recognition and elimination by NK cells decrease Herpes simplex virus 1 is a ubiquitous human pathogen and the cause of several ailments. Enk et al. found that the HSV1-encoded miR H8 targets the GPI anchoring pathway, reducing expression of several immune-modulating proteins, thus enhancing viral spread and enabling evasion of natural killer cell elimination.