ウイルス感染初期の抗ウイルス応答選択機構の解析

宿主细胞激活第一道防御机制，如细胞凋亡或诱导I型干扰素（IFN），以防止病毒感染时的复制和增殖。rig - i样受体（RLRs）识别病毒的单链RNA （ssRNA）或双链RNA (dsRNA)，并与线粒体抗病毒信号（MAVS）结合诱导这些防御反应。在通过MAVS介导病毒先天免疫应答的map3k中，ASK1尤为重要。先前的研究发现凋亡信号调节激酶1 （Apoptosis Signal Regulating Kinase 1, ASK1）在病毒感染时促进I型IFN的表达。然而，目前尚不清楚ASK1如何控制I型IFN的产生。我们的研究发现ASK1促进MAVS的磷酸化。在表达MAVS磷酸化缺陷突变体的mef中，病毒感染后I型IFN的产生被抑制，仙台病毒的复制被促进。这些结果表明，ASK1介导的MAVS磷酸化对病毒感染的保护是必要的。综上所述，我们的研究表明ASK1介导的MAVS磷酸化对于保护宿主细胞免受病毒感染是必要的。

Host cells activate the first line of defense mechanisms, such as apoptosis or induction of type I interferon (IFN), to prevent virus replication and proliferation upon virus infection. RIG-I-like receptors (RLRs) recognize single-stranded RNA (ssRNA) or double-stranded RNA (dsRNA) of viruses, and bind with Mitochondrial antiviral signaling (MAVS) to induce these defense responses. Among the MAP3Ks mediating the innate immune response to viruses via MAVS, ASK1 is particularly important. Previous studies have discovered that Apoptosis Signal Regulating Kinase 1 (ASK1) promotes the expression of type I IFN in response to virus infection. However, it was unclear how ASK1 controls type I IFN production.Our research revealed that ASK1 promotes the phosphorylation of MAVS. In MEFs expressing a MAVS phosphorylation-defective mutant, the production of type I IFN was suppressed and the replication of Sendai virus was promoted upon virus infection. These results suggest that the phosphorylation of MAVS mediated by ASK1 is necessary for protection against virus infection.In summary, our research suggests that the phosphorylation of MAVS mediated by ASK1 is necessary for the protection of host cells against virus infection.