ウイルス感染初期の抗ウイルス応答選択機構の解析

病毒感染早期抗病毒反应选择机制分析

• 批准号: 21J14073
• 负责人: 趙 東儀
• 金额: $ 0.96万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-28 至 2023-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21J14073/
• 关键词: Type I IFN; Apoptosis; MAVS; ASK1

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.

宿主细胞激活第一道防线机制，例如细胞凋亡或诱导 I 型干扰素 (IFN)，以防止病毒感染后的复制和增殖。 RIG-I 样受体 (RLR) 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) 结合以诱导这些防御反应。在通过 MAVS 介导对病毒的先天免疫反应的 MAP3K 中，ASK1 尤其重要。先前的研究发现，细胞凋亡信号调节激酶1（ASK1）会促进I型IFN的表达以应对病毒感染。然而，目前尚不清楚ASK1如何控制I型IFN的产生。我们的研究表明ASK1促进MAVS的磷酸化。在表达 MAVS 磷酸化缺陷突变体的 MEF 中，I 型 IFN 的产生受到抑制，仙台病毒的复制在病毒感染后得到促进。这些结果表明，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。 总之，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。