Hijacking the endosomal mitophagy detour: An ATG16L1-dependent immune evasion pathway in HCV infection

Investigate the hypothesis that HCV routes damaged or signaling-competent mitochondria through an ATG16L1-dependent, ATG5-independent endosomal mitophagy pathway to evade canonical mitophagy checkpoints and suppress antiviral MAVS/IFN signaling. Use mito-QC reporters and targeted recruitment tools in HCV-infected hepatocytes to genetically and pharmacologically separate ATG16L1 versus ATG5 dependence, measuring IFN outputs, inflammasome activity, and viral persistence. Validate this noncanonical mitophagy pathway as a target for peptide or small-molecule inhibitors that disrupt ATG16L1 recruitment or endosomal coupling, offering new host-directed antivirals with minimized toxicity.

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