MARK3 promotes host antiviral defense by driving GEF-H1-mediated TBK1 activation.

MARK3 promotes type I interferon production and broad-spectrum antiviral defense by phosphorylating GEF-H1 at Ser645 to potentiate TBK1 activation and IRF3 phosphorylation.

• Why it matters: Innate antiviral immunity depends on rapid IFN-I signaling, but the upstream kinase regulators that drive TBK1–IRF3 activation are not fully defined.
• What they did: Using in vitro and in vivo models, the study shows MARK3 kinase-dependent antiviral activity through a MARK3–GEF-H1–TBK1 axis, including direct MARK3–GEF-H1 interaction and Ser645 phosphorylation.
• The result: Phosphorylated GEF-H1 enhances TBK1 activation, increases IRF3 phosphorylation and nuclear translocation, and triggers IFN-I induction and downstream ISG expression.