Palmitoylation of glycoproteins under low temperature enhances SVCV replication.

The temperature of water is a crucial factor that affects rhabdovirus infections in fish. Numerous rhabdoviruses, known for their high infectivity at relative low water temperatures (below 20°C), have led to significant economic impacts on global aquaculture. However, the molecular mechanisms underlying their temperature-dependent infectivity and pathogenicity remain unclear. Here, we employed spring viremia of carp virus (SVCV), a rhabdovirus prevalent at low temperatures, as a model. We found that the low temperature markedly elevates levels of palmitic acid in zebrafish, which promotes the palmitoylation of the SVCV glycoprotein (G). This modification enhances stability and cell membrane localization of the G protein, thereby facilitating viral budding. Furthermore, we identified the acyltransferase ZDHHC15a, upregulated at low temperatures, as the mediator of this palmitoylation. A competitive peptide targeting the palmitoylation site of SVCV G exhibited potent antiviral activity. Notably, a similar mechanism was observed in other aquatic rhabdoviruses that are low-temperature susceptible. Overall, our findings elucidate the mechanism underlying the temperature sensitivity of fish rhabdoviruses and hold broader significance for understanding the temperature adaptive evolution of other aquatic viruses.