RIOK1/2 Negatively Regulates the Antiviral Response by Targeting TBK1 in Yellow Catfish (Pelteobagrus fulvidraco)

The yellow catfish (Pelteobagrus fulvidraco) industry has expanded to a certain scale and is an important part of aquaculture in China, but frequent diseases have caused huge economic losses. Comprehending the fish's immune mechanisms, particularly the regulation of the interferon (IFN) response, is of paramount importance for future drug development and disease-resistant molecular breeding. Notably, the role of atypical protein kinases, such as the RIO kinase family, in immune regulation is poorly defined. Here, we investigated the roles of yellow catfish RIO kinases, PfRIOK1 and PfRIOK2, in modulating the IFN response through their interaction with PfTBK1, a key player in the RLR signaling pathway. Mechanically, PfRIOK1 and PfRIOK2 negatively regulate the IFN response by interacting with the RIO domains to target and degrade PfTBK1. Our findings reveal that the overexpression of PfRIOK1 and PfRIOK2 led to the decreased expression of IFN-related genes and enhanced viral replication in vitro. Additionally, PfRIOK1 and PfRIOK2 could inhibit PfTBK1-mediated antiviral responses in infected cells. These results suggest that PfRIOK1 and PfRIOK2 act as negative regulators of the IFN response in yellow catfish, providing new insights into the regulatory mechanisms of fish innate immunity and offering target molecules for molecular design breeding in aquaculture.