Oshiumi Hiroyuki, Matsumoto Misako, Seya Tsukasa
Graduate School of Medicine, Hokkaido University.
Uirusu. 2011 Dec;61(2):153-61. doi: 10.2222/jsv.61.153.
Viral RNA is recognized by RIG-I-like receptors and Toll-like receptors. RIG-I is a cytoplasmic viral RNA sensor. High Mobility Group Box (HMGB) proteins and DExD/H box RNA helicases, such as DDX3 and 60, associate with viral RNA. Those proteins promotes the RIG-I binding to viral RNA. RIG-I triggers the signal via IPS-1 adaptor molecule to induce type I IFN. RIG-I harbors Lys63-linked polyubiquitination by Riplet and TRIM25 ubiquitin ligases. The polyubiquitination is essential for RIG-I-mediated signaling. Toll-like receptors are located in endosome. TLR3 recognizes viral double-stranded RNA, and TLR7 and 8 recognize single-strand RNA. Virus has the ability to suppress these innate immune response. For example, to inhibit RIG-I-mediated signaling, HCV core protein suppresses the function of DDX3. In addition, HCV NS3-4A protein cleaves IPS-1 to inhibit the signal. Molecular mechanism of how viral RNA is recognized by innate immune system will make great progress on our understanding of how virus escapes from host immune system.
病毒RNA可被视黄酸诱导基因I样受体(RIG-I样受体)和Toll样受体识别。RIG-I是一种细胞质病毒RNA传感器。高迁移率族蛋白盒(HMGB)蛋白以及DExD/H盒RNA解旋酶,如DDX3和60,可与病毒RNA结合。这些蛋白促进RIG-I与病毒RNA的结合。RIG-I通过接头分子IPS-1触发信号以诱导I型干扰素。RIG-I通过Riplet和TRIM25泛素连接酶进行K63连接的多聚泛素化修饰。这种多聚泛素化修饰对于RIG-I介导的信号传导至关重要。Toll样受体位于内体中。TLR3识别病毒双链RNA,而TLR7和TLR8识别单链RNA。病毒具有抑制这些先天免疫反应的能力。例如,为了抑制RIG-I介导的信号传导,丙型肝炎病毒核心蛋白会抑制DDX3的功能。此外,丙型肝炎病毒NS3-4A蛋白会切割IPS-1以抑制信号。先天免疫系统识别病毒RNA的分子机制将极大地推动我们对病毒如何逃避宿主免疫系统的理解。