march2 negatively regulates antiviral immune response by targeting tbk1 in grass carp (Ctenopharyngodon idella)

Grass carp is one of the most economically important fish species. Hemorrhagic diseases caused by grass carp reovirus (GCRV) can seriously damage the economic yield of grass carp. Therefore, antiviral research on grass carp is urgently needed. Membrane-associated RING-CH2 (MARCH2) negatively regulates the innate immune response in mice. However, little is known about the role of march2 in the antiviral innate immune response in teleost fish. Our present study showed that march2 has high homology in grass carp, its orthologs, and mammals, and has the same amino acid sequence in grass carp and crucian carp. Overexpression of Cimarch2 (Ctenopharyngodon idella march2) significantly inhibited interferon (IFN) activation induced by Polyinosinic-polycytidylic acid (poly I: C), spring viremia of carp virus (SVCV), and GCRV. However, knocking down Cimarch2 enhanced the activation of IFN induced by poly I: C, SVCV, and GCRV. Overexpression of Cimarch2 can promotes viral replication. Mechanistically, Cimarch2 tightly bound to TANK-binding kinase 1 (tbk1) and downregulated tbk1 through the proteasome pathway. Our results demonstrated the potential role of Cimarch2 in the antiviral breeding of grass carp.