Lactylation of its phosphoprotein interferes with the replication of the spring viremia of carp virus.

The metabolic by-product of glycolysis, lactate, and lactylation-mediated protein modification are involved in various biological processes, including host antiviral responses. The spring viremia of carp virus (SVCV), a rhabdovirus that devastates aquaculture, relies on its multifunctional phosphoprotein (P) for replication and evasion of the host immune system. In this study, we found that SVCV infection increased lactate levels in zebrafish, with lactate modulating SVCV proliferation through lactylation of the viral P protein. ldha-null zebrafish exhibited reduced lactate levels and increased susceptibility to SVCV. Conversely, sodium lactate supplementation suppressed viral replication and improved the survival rate of infected zebrafish. Furthermore, we identified lactylation sites in the SVCV P protein. These findings revealed that lactate-mediated lactylation is a host defense mechanism against SVCV and could provide novel strategies for antiviral intervention in aquaculture.IMPORTANCELactylation is an emerging post-translational modification, yet its presence in viruses has rarely been investigated. This study identified the lactylation modification sites in the spring viremia of carp virus (SVCV) P protein and demonstrated that adding sodium lactate modifies the P protein and reduces SVCV replication. These results suggest that sodium lactate has antiviral properties and plays an important role in combating SVCV infection, while also revealing a novel modification of the SVCV viral protein within the host.