Guo Zhu, Chen Li-mei, Zeng Hui, Gomez Jorge A, Plowden Julie, Fujita Takashi, Katz Jacqueline M, Donis Ruben O, Sambhara Suryaprakash
Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Am J Respir Cell Mol Biol. 2007 Mar;36(3):263-9. doi: 10.1165/rcmb.2006-0283RC. Epub 2006 Oct 19.
Retinoic acid-inducible gene I (RIG-I) has recently been identified as one of the key intracellular sensors of virus infection. RIG-I binds to cytosolic double-stranded RNA and initiates a signaling cascade that leads to the activation of transcription factors required for expression of type I interferon (IFN-I). Previous evidence suggests that nonstructural protein 1 (NS1) encoded by influenza A virus (IAV) suppresses IFN-I secretion in virus-infected cells by an unknown mechanism. In the present study, we demonstrate that RIG-I is required for induction of IFN-I in an IAV-infected human lung epithelial cell line. Knockdown of RIG-I expression by RNA interference greatly impairs production of IFN-beta in cells infected with different strains of wild-type IAV. Furthermore, co-expression of IAV NS1 down-regulates production of IFN-beta induced by RIG-I agonists, and ectopic expression of RIG-I inhibits the replication of IAV. These results provide further information on the mechanism by which IAV NS1 antagonizes the host antiviral response.
视黄酸诱导基因I（RIG-I）最近被确定为病毒感染的关键细胞内传感器之一。RIG-I与细胞质双链RNA结合，并启动信号级联反应，导致I型干扰素（IFN-I）表达所需的转录因子激活。先前的证据表明，甲型流感病毒（IAV）编码的非结构蛋白1（NS1）通过未知机制抑制病毒感染细胞中IFN-I的分泌。在本研究中，我们证明RIG-I是IAV感染的人肺上皮细胞系中诱导IFN-I所必需的。通过RNA干扰敲低RIG-I的表达会极大地损害感染不同野生型IAV株的细胞中IFN-β的产生。此外，IAV NS1的共表达下调了RIG-I激动剂诱导的IFN-β的产生，并且RIG-I的异位表达抑制了IAV的复制。这些结果为IAV NS1拮抗宿主抗病毒反应的机制提供了进一步的信息。
