An Identical miRNA of the Human JC and BK Polyoma Viruses Targets the Stress-Induced Ligand ULBP3 to Escape Immune Elimination
An Identical miRNA of the Human JC and BK Polyoma Viruses Targets the Stress-Induced Ligand ULBP3 to Escape Immune Elimination
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DOI：
10.1016/j.chom.2011.01.008
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发表时间：
2011-02-17
影响因子：
30.3
通讯作者：
Mandelboim, Ofer
中科院分区：
文献类型：
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作者：
Bauman, Yoav;Nachmani, Daphna;Mandelboim, Ofer
人类多瘤病毒JCV和BKV在65%-90%的人类中建立无症状的持续感染，但在免疫抑制条件下可导致严重疾病。这些病毒逃避免疫识别的机制尚不清楚。在这里，我们证明了在JCV和BKV之间序列相同的病毒miRNA靶向应激诱导的配体ULBP3，这是一种被杀手受体NKG2D识别的蛋白质。因此，病毒miRNA介导的ULBP3下调导致NKG2D介导的自然杀伤(NK)细胞对病毒感染细胞的杀伤减少。重要的是，当病毒miRNA的活性在感染过程中被抑制时，NK细胞可以更有效地杀死受感染的细胞。由于NKG2D也由各种T细胞亚群表达，我们认为JCV和BKV使用相同的针对ULBP3的miRNA来逃避先天性和获得性免疫系统的检测，解释了这些病毒如何在不被免疫系统消除的情况下保持潜伏状态。
The human polyoma viruses JCV and BKV establish asymptomatic persistent infection in 65%-90% of humans but can cause severe illness under immunosuppressive conditions. The mechanisms by which these viruses evade immune recognition are unknown. Here we show that a viral miRNA identical in sequence between JCV and BKV targets the stress-induced ligand ULBP3, which is a protein recognized by the killer receptor NKG2D. Consequently, viral miRNA-mediated ULBP3 downregulation results in reduced NKG2D-mediated killing of virus-infected cells by natural killer (NK) cells. Importantly, when the activity of the viral miRNA was inhibited during infection, NK cells killed the infected cells more efficiently. Because NKG2D is also expressed by various T cell subsets, we propose that JCV and BKV use an identical miRNA that targets ULBP3 to escape detection by both the innate and adaptive immune systems, explaining how these viruses remain latent without being eliminated by the immune system.