State Key Laboratory of Agriculture Microbiology, Huazhong Agricultural University, Wuhan, 430070, PR China; Division of Animal Infectious Diseases, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
Hubei Colorectal Cancer Clinical Research Center, Hubei Cancer Hospital, Wuhan, 430071, China.
Virology. 2019 Sep;535:122-129. doi: 10.1016/j.virol.2019.06.017. Epub 2019 Jun 28.
Seneca Valley virus (SVV) is a member of the Picornaviridae family, which has been used to treat neuroendocrine cancer. The innate immune system plays an important role in SVV infection. However, few studies have elucidated the relationship between SVV infection and the host's antiviral response. In this study, SVV replication could induce the degradation of RIG-I in HEK-293T, SW620 and SK6 cells. And overexpressing retinoic acid-inducible gene I (RIG-I) could significantly inhibit SVV propagation. The viral protein 2C and 3C were essential for the degradation of RIG-I. Furthermore, 2C and 3C significantly reduced Sev or RIG-I-induced IFN-β production. Mechanistically, 2C and 3C induced RIG-I degradation through the caspase signaling pathway. Taken together, we demonstrate the antiviral role of RIG-I against SVV and the mechanism by which SVV 2C and 3C weaken the host innate immune system.
森那布病毒(SVV)是微小核糖核酸病毒科的一种成员,已被用于治疗神经内分泌肿瘤。先天免疫系统在 SVV 感染中起着重要作用。然而,很少有研究阐明 SVV 感染与宿主抗病毒反应之间的关系。在这项研究中,SVV 复制可以诱导 HEK-293T、SW620 和 SK6 细胞中 RIG-I 的降解。并且过表达视黄酸诱导基因 I(RIG-I)可以显著抑制 SVV 的复制。病毒蛋白 2C 和 3C 对于 RIG-I 的降解是必需的。此外,2C 和 3C 显著降低了 Sev 或 RIG-I 诱导的 IFN-β 的产生。在机制上,2C 和 3C 通过半胱天冬酶信号通路诱导 RIG-I 降解。总之,我们证明了 RIG-I 对 SVV 的抗病毒作用,以及 SVV 2C 和 3C 削弱宿主先天免疫系统的机制。