Reversible protein S-palmitoylation, mediated by protein acyl transferases (PATs) and depalmitoylases, is essential for regulating numerous biological processes, including subcellular localization, protein stability, enzymatic activity, and protein-protein interactions. While the study of S-palmitoylation in virology is extensive, less attention has been paid to its reverse process, depalmitoylation, at the virus-host interface. This review summarizes the dynamic regulatory mechanisms of both S-palmitoylation and depalmitoylation. We systematically review the functional consequences of these host enzyme-mediated modifications based on the roles of viral proteins in the viral life cycle. Next, we focus on how viruses exploit these modifications for immune evasion and the corresponding host antiviral strategies. Finally, we analyze the distinct role of depalmitoylation in regulating viral replication and host defense. Overall, this review aims to provide new insights into the regulatory mechanisms of reversible S-palmitoylation at the virus-host interface.
Xu et al. (Wed,) studied this question.