SIRT5-mediated desuccinylation of the porcine deltacoronavirus M protein drives pexophagy to enhance viral proliferation.

ABSTRACT: Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus capable of infecting various animal species, including humans. In this study, we explored the roles of sirtuins (SIRTs), a conserved family of protein deacylases and mono-adenosine diphosphate-ribosyltransferases, in PDCoV replication. Surprisingly, we found that SIRT5-a unique member of SIRTs with distinct desuccinylation, demalonylation, and deglutarylation activities-is a proviral factor essential for PDCoV replication; its catalytic activities are crucial in this process. Mechanistically, SIRT5 interacts with and desuccinylates the PDCoV membrane (M) protein. This modification activates the ataxia-telangiectasia mutated (ATM) pathway, facilitates ubiquitination of peroxisomal biogenesis protein 5 (PEX5), and r

SUBMITTER: Li Z 

PROVIDER: S-EPMC12143549 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature