Host immune system gene targeting by a viral miRNA
Host immune system gene targeting by a viral miRNA
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DOI：
10.1126/science.1140956
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发表时间：
2007-07-20
期刊：
影响因子：
56.9
通讯作者：
Mandelboim, Ofer
中科院分区：
文献类型：
--
作者：
Stern-Ginossar, Noam;Elefant, Naama;Mandelboim, Ofer
最近在疱疹病毒中发现了病毒编码的微小RNA（miRNAs）。然而，它们的生物学作用大多是未知的。我们开发了一种用于预测miRNA靶点的算法，并将其应用于人巨细胞病毒miRNA，从而将主要组织相容性复合物I类相关链B（MIC B）基因鉴定为hcmv-miR-UL 112的首选候选靶点。MICB是自然杀伤（NK）细胞活化受体NKG 2D的应激诱导配体，对NK细胞杀伤病毒感染细胞和肿瘤细胞至关重要。我们发现hcmv-miR-UL 112在病毒感染期间特异性下调MICB表达，导致NKG 2D结合减少和NK细胞杀伤减少。我们的研究结果揭示了一个基于miRNA的免疫逃避机制，似乎是利用人类巨细胞病毒。
Virally encoded microRNAs (miRNAs) have recently been discovered in herpesviruses. However, their biological roles are mostly unknown. We developed an algorithm for the prediction of miRNA targets and applied it to human cytomegalovirus miRNAs, resulting in the identification of the major histocompatibility complex class I-related chain B (MICB) gene as a top candidate target of hcmv-miR-UL112. MICB is a stress-induced ligand of the natural killer (NK) cell activating receptor NKG2D and is critical for the NK cell killing of virus-infected cells and tumor cells. We show that hcmv-miR-UL112 specifically down-regulates MICB expression during viral infection, leading to decreased binding of NKG2D and reduced killing by NK cells. Our results reveal a miRNA-based immunoevasion mechanism that appears to be exploited by human cytomegalovirus.