Influenza virus infection activates TAK1 to suppress RIPK3-independent apoptosis and RIPK1-dependent necroptosis.

ABSTRACT: Many DNA viruses develop various strategies to inhibit cell death to facilitate their replication. However, whether influenza A virus (IAV), a fast-replicating RNA virus, attenuates cell death remains unknown. Here, we report that IAV infection induces TAK1 phosphorylation in a murine alveolar epithelial cell line (LET1) and a murine fibroblastoma cell line (L929). The TAK1-specific inhibitor 5Z-7-Oxzeneonal (5Z) and TAK1 knockout significantly enhance IAV-induced apoptosis, as evidenced by increased PARP, caspase-8, and caspase-3 cleavage. TAK1 inhibition also increases necroptosis as evidenced by increased RIPK1^S166, RIPK3^T231/S232, and MLKL^S345 phosphorylation. Mechanistically, TAK1 activates IKK, which phosphorylates RIPK1^S25 and inhibits its

SUBMITTER: Sun Y 

PROVIDER: S-EPMC11264382 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature