Nakhaei Peyman, Genin Pierre, Civas Ahmet, Hiscott John
The Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Quebec, Canada.
Semin Immunol. 2009 Aug;21(4):215-22. doi: 10.1016/j.smim.2009.05.001. Epub 2009 Jun 17.
Viral and microbial pathogens contain specific motifs or pathogen-associated molecular patterns (PAMPs) that are recognized by cell surface- and endosome-associated Toll-like receptors (TLRs). RNA virus infection is also detected through TLR-independent mechanisms. Early viral replicative intermediates are detected by two recently characterized cystolic viral RNA receptors-RIG-I and MDA-5. Both are DExDH/box RNA helicases, and RIG-I specifically recognizes 5'-triphosphate containing viral RNA and transmits signals that induce type I interferon-mediated host immunity against virus infection. In this review, we will focus on RIG-I-like receptor (RLR) signal transduction and the regulatory mechanisms - ubiquitination, deubiquitination, ISGylation - underlying this important host response.
病毒和微生物病原体含有特定基序或病原体相关分子模式(PAMP),可被细胞表面和内体相关的Toll样受体(TLR)识别。RNA病毒感染也可通过不依赖TLR的机制被检测到。早期病毒复制中间体可被最近鉴定的两种胞质病毒RNA受体——视黄酸诱导基因I(RIG-I)和黑色素瘤分化相关基因5(MDA-5)检测到。二者均为DExDH/盒RNA解旋酶,RIG-I特异性识别含5'-三磷酸的病毒RNA,并传递诱导I型干扰素介导的宿主抗病毒感染免疫的信号。在本综述中,我们将聚焦于RIG-I样受体(RLR)信号转导以及这一重要宿主反应背后的调控机制——泛素化、去泛素化、ISGylation。