Discovering broader antiviral strategies:Role of interferon-induced transmembrane proteins in virus infection

Host antiviral strategies have been studied for a long time,and the antibody response and T-cell response represent the classic host antiviral strategies.The entry of enveloped viruses into host cells is a complex process that could involve interactions ofmultiple viral glycoproteins and host-cell receptors.Blocking this process is the key to preventing infection.In general,antigenspecific neutralizing antibodies are thought to effectively bind to viral glycoproteins to block virus entry.However,there are other unknown host factors that inhibit or enhance the virus entry into the host cell.Recently,Yang et al.discovered that interferon-induced transmembrane protein-1(IFITM1)inhibited Epstein–Barr virus(EBV)infection in epithelial cells(ECs)by competing with viral glycoproteins to bind to Ephrin receptor A2(EphA2),thereby blocking this key entry receptor[1](Figure 1).Together with previous research,this finding hints at the importance of discovering broader host protective factors.ECs are known to be critical sites for EBV infection and replication.EphA2 has been reported as one of the most crucial EBV entry receptors on the EC surface,which binds to viral glycoprotein H/L(gH/gL)and glycoprotein B(gB)[2]to drive the internalization and fusion of EBV[3].However,ECs with low susceptibility to EBV can still express a high level of EphA2[4],raising questions about additional factors that influence host susceptibility.