부산대학교 도서관

Plus-stranded RNA viruses have limited coding capacity and have to co-opt numerous pro-viral host factors to support their replication. Many of the co-opted host factors support the biogenesis of the viral replication compartments and the formation of viral replicase complexes on subverted subcellular membrane surfaces. Tomato bushy stunt virus (TBSV) exploits peroxisomal membranes, whereas the closely-related carnation Italian ringspot virus (CIRV) hijacks the outer membranes of mitochondria. How these organellar membranes can be recruited into pro-viral roles is not completely understood. Here, we show that the highly conserved Fis1 mitochondrial fission protein is co-opted by both TBSV and CIRV via direct interactions with the p33/p36 replication proteins. Deletion of FIS1 in yeast or knockdown of the homologous Fis1 in plants inhibits tombusvirus replication. Instead of the canonical function in mitochondrial fission and peroxisome division, the tethering function of Fis1 is exploited by tombusviruses to facilitate the subversion of membrane contact site (MCS) proteins and peroxisomal/mitochondrial membranes for the biogenesis of the replication compartment. We propose that the dynamic interactions of Fis1 with MCS proteins, such as the ER resident VAP tethering proteins, Sac1 PI4P phosphatase and the cytosolic OSBP-like oxysterol-binding proteins, promote the formation and facilitate the stabilization of virus-induced vMCSs, which enrich sterols within the replication compartment. We show that this novel function of Fis1 is exploited by tombusviruses to build nuclease-insensitive viral replication compartment. Author summary: Positive-strand RNA viruses, which include many dangerous pathogens of animals and plants, require the biogenesis of viral replication compartments. Utilizing TBSV and the model host yeast, we found a critical and novel role for the Fis1 mitochondrial fission protein. The pro-viral function of Fis1 is manifested through binding to the TBSV p33 replication protein that results in recruitment into the replication compartment formed from aggregated peroxisomes. Fis1 also binds to the related carnation Italian ringspot virus (CIRV) p36 replication protein in the replication compartment formed from aggregated mitochondria. Instead of the canonical function in mitochondria fission or peroxisome division, the tethering function of Fis1 is exploited by TBSV in facilitating the recruitment of cellular membrane contact site proteins into the viral replication compartment. Altogether, co-opting Fis1 is critical for tombusviruses to build their replication compartments in infected cells. Targeting these organelle-tethering proteins by inhibitors or other ways could open up new antiviral strategies. [ABSTRACT FROM AUTHOR]