Duck HERC3 Positively Regulates RIG-I/MAVS-Mediated IFN-β Production Through Interaction with MAVS

The RIG-I-like receptor (RLR) pathway is essential for detecting cytosolic viral RNA and initiating type I interferon responses via the key adaptor MAVS. Although MAVS regulation has been extensively studied in mammals, little is known about its regulatory mechanisms in avian species. HERC3 participates in the regulation of RLR-mediated immunity in mammals, but its role in ducks remains unexplored. Here, we investigated the function of duck HERC3 (duHERC3) in the RLR pathway. We found that duHERC3 was ubiquitously expressed in all examined tissues and significantly upregulated upon Newcastle disease virus (NDV) infection and 3p-hpRNA stimulation. Overexpression of duHERC3 elevated the mRNA levels of MAVS and OASL and enhanced IFN-β production, whereas knockdown of duHERC3 exerted opposite effects. Co-immunoprecipitation (Co-IP) revealed that duHERC3 interacts with the N-terminal domain of MAVS (aa5-175). Moreover, duHERC3 enhanced MAVS-mediated IFN-β induction in a RIG-I-dependent manner, indicating that duHERC3 functions through the canonical RIG-I-MAVS axis. Collectively, our findings demonstrate that duck HERC3 positively regulates MAVS-dependent IFN-β production via interaction with MAVS, providing new insights into the regulatory network of avian innate immunity.