Barral Paola M, Sarkar Devanand, Fisher Paul B, Racaniello Vincent R
Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, 1101 East Marshall Street, Sanger Hall Building, Room 11-015, Richmond, VA 23298-0033, USA.
Virology. 2009 Sep 1;391(2):171-6. doi: 10.1016/j.virol.2009.06.045. Epub 2009 Jul 22.
The innate immune system senses RNA virus infections through membrane-bound Toll-like receptors or the cytoplasmic proteins RIG-I and MDA-5. RIG-I is believed to recognize the 5'-triphosphate present on many viral RNAs, and hence is important for sensing infections by paramyxoviruses, influenza viruses, rhabdoviruses, and flaviviruses. MDA-5 recognizes dsRNA, and senses infection with picornaviruses, whose RNA 5'-ends are linked to a viral protein, VPg, not a 5'-triphosphate. We previously showed that MDA-5 is degraded in cells infected with different picornaviruses, and suggested that such cleavage might be a mechanism to antagonize production of type I IFN in response to viral infection. Here we examined the state of RIG-I during picornavirus infection. RIG-I is degraded in cells infected with poliovirus, rhinoviruses, echovirus, and encephalomyocarditis virus. In contrast to MDA-5, cleavage of RIG-I is not accomplished by cellular caspases or the proteasome. Rather, the viral proteinase 3C(pro) cleaves RIG-I, both in vitro and in cells. Cleavage of RIG-I during picornavirus infection may constitute another mechanism for attenuating the innate response to viral infection.
天然免疫系统通过膜结合的Toll样受体或细胞质蛋白RIG-I和MDA-5来感知RNA病毒感染。据信，RIG-I能够识别许多病毒RNA上存在的5'-三磷酸，因此对于感知副粘病毒、流感病毒、弹状病毒和黄病毒的感染非常重要。MDA-5识别双链RNA，并感知小RNA病毒的感染，其RNA 5'-末端与病毒蛋白VPg相连，而非5'-三磷酸。我们之前发现，MDA-5在感染不同小RNA病毒的细胞中会发生降解，并提出这种切割可能是一种对抗病毒感染时I型干扰素产生的机制。在此，我们研究了小RNA病毒感染期间RIG-I的状态。RIG-I在感染脊髓灰质炎病毒、鼻病毒、艾柯病毒和脑心肌炎病毒的细胞中会发生降解。与MDA-5不同，RIG-I的切割不是由细胞半胱天冬酶或蛋白酶体完成的。相反，病毒蛋白酶3C(pro)在体外和细胞中均可切割RIG-I。小RNA病毒感染期间RIG-I的切割可能构成了另一种减弱对病毒感染的天然免疫反应的机制。
