Fatty Acid Synthase Promotes the Palmitoylation of Chikungunya Virus nsP1

S-palmitoylation is an important form of lipid posttranslational modification, which affects the function of proteins by regulating their transport, stability, and localization. Previous studies have shown that FASN is critical for CHIKV replication; however, the mechanism for this function of FASN remains unknown. The key zinc finger DHHC domain-containing palmitoyltransferases involved in the palmitoylation of nsP1 are not clear. We demonstrated that FASN promoted CHIKV replication through nsP1 palmitoylation. ZDHHC2 and ZDHHC19 were identified as the major enzymes for nsP1 palmitoylation. Since nsP1 proteins are conserved in alphaviruses, our results highlight the mechanisms by which alphavirus nsP1 is palmitoylated.