IFIT8 inhibits GCRV replication by suppressing protein translation through interaction with EIF4A in grass carp (Ctenopharyngodon idella).

Abstract

Interferon regulatory proteins have a key effect on the host's antiviral immunity. Many interferon regulatory proteins have been identified, yet the functions and mechanisms of most of them in antiviral immunity are still unclear. Our study shows that interferon-induced protein 8 (IFIT8), which contains tetratricopeptide repeat sequences, restricts Grass Carp Reovirus (GCRV) replication by directly interacting with eukaryotic initiation factor 4A (EIF4A). CiIFIT8 displays widespread expression in all tested tissues, and it is most strongly expressed in muscle, while its expression increases after GCRV infection. Overexpression of CiIFIT8 in cells reduces GCRV replication. The use of the EIF4A inhibitor Rocaglamide (Roc-A) verified that CiEIF4A is necessary for GCRV replication. During viral infection, CiIFIT8 associates with CiEIF4A, interrupting EIF4A-mediated initiation of protein translation, lowering EIF4A-dependent protein synthesis during GCRV replication, and consequently inhibiting viral replication. Overall, our results suggest that IFIT8 performs its antiviral function through EIF4A.