TRIM34 modulates influenza virus-activated programmed cell death by targeting Z-DNA-binding protein 1 for K63-linked polyubiquitination

• DOI: 10.1016/j.jbc.2022.101611
• Publication Date: 2022-01-20T15:56:58Z
• Authors: Xiaoyan Wang; Jing Xiong; Diwei Zhou; Shanfeng Zhang; Li Wang; Qingqing Tian; Changming Li; Jie Liu; Yaping Wu; Junying Li; Jun Wang
• Keywords: 0301 basic medicine; Ubiquitination; RNA-Binding Proteins; Apoptosis; 3. Good health; DNA-Binding Proteins; Mice; 03 medical and health sciences; Orthomyxoviridae Infections; Influenza A virus; Influenza, Human; Animals; Humans; Carrier Proteins; Research Article

Z-DNA-binding protein 1 (ZBP1) is an innate sensor of influenza A virus (IAV) that participates in IAV-induced programmed cell death. Nevertheless, little known about the upstream signaling pathways regulating ZBP1. We found a member tripartite motif (TRIM) family, TRIM34, interacted with ZBP1 to promote its K63-linked polyubiquitination. Using series genetic approaches, we provide vitro and vivo evidence indicating IAV triggered death inflammatory responses via dependent on TRIM34/ZBP1 interaction. TRIM34 expression interaction protected mice from during infection owing reduced epithelial damage. Additionally, analysis clinical samples revealed associates mediates polyubiquitination vivo. Higher levels proinflammatory cytokines correlated higher IAV-infected patients. Taken together, conclude serves as critical regulator by mediating