The critical x[I/L]xbS motif in adaptor proteins, MAVS, MITA, and TRIF contributes to type I IFN production and antiviral immune response in fish.

Mammalian antiviral signaling adaptors, such as MAVS, MITA, and TRIF, have been shown to possess a conserved pLxIS motif (p, hydrophilic residue; L, leucine; x, any residue; I, isoleucine; S, serine, phosphorylation site), which has been identified as the key site leading to the transduction of antiviral signaling. But, the antiviral activity of the potential pLxIS motif in these homologous adaptors remains to be fully elucidated in fish. In this study, teleost TRIF, MAVS and MITA were found to contain conserved motifs with respective consensus sequences p[I/L]E[I/V]S, xLxbS and p[I/L]xbS (E, glutamic acid; V, valine, b, hydrophobic residue). Furthermore, these three adaptor proteins share a universal x[I/L]xbS structural motif, wherein the internal serine residue serves as an indispensable and highly conserved functional site. Functional assays revealed that the x[I/L]xbS motif promotes antiviral immune responses mediated by fish MAVS, MITA and TRIF, by inducing the expression of type I IFNs and ISGs as well as the activation of IRF3. Thus, the present study may shed light on the functional evolution of antiviral immune signaling of the conserved motif of these adaptors in teleost.