非洲猪瘟病毒pA179L异戊二烯化修饰鉴定及对细胞凋亡的影响OA

Protein prenylation refers to the covalent attachment of farnesyl or geranylgeranyl isoprenoid groups to proteins that have a CAAX motif at their carboxyl termini,where C is an invariant cysteine,A1 and A2 are usually aliphatic residues,and X can be any amino acid.This study investigated the relationship between prenylation modification of the African swine fever virus-encoded pA179L protein and its inhibition of apoptosis.Using the PrePS program prediction and farnesyl antibody,it was demonstrated that pA179Lhad undergone prenylation.In this study,the CNLI motif of pA179L was mutated to SNLI or deleted for comparison of their localization.Analyses of nuclear-cytoplasmic separation,immunoblotting and indirect immunofluorescence assays revealed that prenylation regulated pA179L localization.Three prenylation inhibitors were used to demonstrate that pA179L mainly undergwent geranylgeranylation.This study also compared the inhibitory effects on apoptosis and mitochondrial localization between wild-type pA179L and its prenylation-deficient mutant pA179L-C176S.The results showed that wild-type pA179L targeted mitochondria via prenylation to inhibit apoptosis whereas the prenylation-deficient mutant pA179L-C176S lost its apoptotic inhibition due to its inability to anchor to mitochondria.This study elucidated the role of ASFV-encoded protein isoprenylation modification in regulating apoptosis,laying a foundation for in-depth understanding of ASFV pathogenesis.