Swine influenza, caused by swine influenza A virus (swIAV), is an acute respiratory viral illness. Although several host factors have been identified that influence swIAV replication, the role of CD46 in this process remains unclear. Here, researchers demonstrate that CD46 inhibits swIAV replication by promoting type I interferon (IFN) production in porcine kidney cells (PK-15). Viral infection of CD46-overexpressing PK-15 cells demonstrated inhibition of H1N1 and H3N2 influenza virus (swIAV) replication and enhanced production of type I IFNs (IFN-α, IFN-β), interferon regulatory factor (IRF) 3, and mitochondrial antiviral signaling protein (MAVS). Viral infection of CD46-knockout PK-15 cells exhibited the opposite effect. Further results showed that CD46 knockout PK-15 cells had better influenza virus proliferation capacity than MDCK cells and PK-15 cells. These results indicate that CD46 is a promising target for regulating swIAV replication and will help develop new drugs to prevent viral infection and replication.
To determine whether CD46 regulates IFN expression during swIAV infection, CD46-KO, CD46-overexpressing, and WT PK-15 cells were infected with swIAV, and IFN expression was assessed by qRT-PCR. H1N1 infection experiments in CD46-KO PK-15 cells showed decreased expression of IFN-α, IFN-β, and mitochondrial antiviral signaling protein (MAVS) compared with WT PK-15 cells; whereas in CD46-overexpressing cells, expression of IFN-α, IFN-β, IRF3, and MAVS was increased compared with WT PK-15 cells (Figure 1A). H3N2 infection experiments in CD46-KO PK-15 cells showed that the expression of IFN-α and IFN-β was reduced at 12 hours compared with WT PK-15 cells; infection experiments in CD46-overexpressing cells showed that the expression of IFN-α, IFN-β, IRF3, and MAVS was increased compared with WT PK-15 cells (Figure 1B), especially IFN-β expression in cells infected with H1N1 and H3N2 viruses. These results suggest that CD46 knockout cell lines may promote the replication ability of swIAV by inhibiting the expression of IFN-α, IFN-β, IRF3, and MAVS.
Figure 1. CD46 suppresses the expression of IFNs in swIAVs infection. (Li H, et al., 2024)