GMPR2-MDA5 Interaction Bridged the Cell Junction and Anti-Gcrv Immune

As a consequence of increased vascular endothelial permeability and vascular injury caused by GCRV (grass carp reovirus) infection, grass carp (Ctenopharyngodon idellus) could suffer from hemorrhagic disease and even death. MDA5 is a key RNA sensor that stimulates type I interferon as well as regulates vascular permeability. The guano monophosphate ductase 2 (GMPR2) plays a key role in regulating the permeability of vascular endothelial cells. This study examined the interaction between grass carp MDA5 and GMPR2 and their antiviral effects. GMPR2 interacted directly with MDA5 and promoted its protein level, whilst MDA5 conversely inhibited the GMPR2 protein expression. The expression of GCRV VP7 protein was inhibited by the increased levels of MDA5 and GMPR2. In addition, the cell junction molecule Claudin7b which is closely related to the change in vascular permeability, was inhibited by both MDA5 and GMPR2. Finally, in GMPR2 knockout zebrafish, the mRNA level of MDA5 was significantly down-regulated, which validated the positive functional relationship of GMPR2 on MDA5. Consistent changes of the Claudin 7b and VP7 protein levels were observed in the GMPR2 and MDA5 overexpression groups. In summary, MDA5-GMPR2 interaction affecting GCRV replication might through cell junction molecule Claudin7b. The results from this study provided systematic support for revealing the genetic basis of cell permeability change as well as the hemorrhagic diseases in grass carp.