病毒复制复合体与磷脂酰乙醇胺

donggua

Plants, animals, and humans are threatened by positive-stranded RNA viruses, which are one of the major groups of intracellular pathogens. To support robust virus replication, these viruses subvert intracellular membranes and co-opt host proteins into virus-induced replication compartments. Tomato bushy stunt virus (TBSV) is a model virus used in yeast to dissect the roles of lipids and proteins in virus replication. In this work, the authors show that one of the two TBSV replication proteins interacts with the guanosine triphosphate (GTP)-bound Rab5 small GTPase, which allows the virus to take advantage of phosphatidylethanolamine (PE)-rich endosomes to build viral replication compartments consisting of peroxisomes. Peak level of TBSV replication depends on the co-opted abundant PE-rich Rab5-positive membranes in plants, too.
威胁人类、动物和植物的正单链RNA病毒是一类重要的细胞内病原物。为保证自身的复制，病毒必须需要同寄主互作，利用病毒的寄主来形成病毒诱导的复制复合体。下面的文章结果表明Tomato bushy stunt virus 复制蛋白通过与寄主TRab5 小GTPase互作来利用寄主富集磷脂酰乙醇胺的内体来构建病毒复制复合体。



Abstract

Positive-strand RNA viruses build extensive membranous replication compartments to support replication and protect the virus from antiviral responses by the host. These viruses require host factors and various lipids to form viral replication complexes (VRCs). The VRCs built by Tomato bushy stunt virus (TBSV) are enriched with phosphatidylethanolamine (PE) through a previously unknown pathway. To unravel the mechanism of PE enrichment within the TBSV replication compartment, in this paper, the authors demonstrate that TBSV co-opts the guanosine triphosphate (GTP)-bound active form of the endosomal Rab5 small GTPase via direct interaction with the viral replication protein. Deletion of Rab5 orthologs in a yeast model host or expression of dominant negative mutants of plant Rab5 greatly decreases TBSV replication and prevents the redistribution of PE to the sites of viral replication. We also show that enrichment of PE in the viral replication compartment is assisted by actin filaments. Interestingly, the closely related Carnation Italian ringspot virus, which replicates on the boundary membrane of mitochondria, uses a similar strategy to the peroxisomal TBSV to hijack the Rab5-positive endosomes into the viral replication compartments. Altogether, usurping the GTP-Rab5–positive endosomes allows TBSV to build a PE-enriched viral replication compartment, which is needed to support peak-level replication. Thus, the Rab family of small GTPases includes critical host factors assisting VRC assembly and genesis of the viral replication compartment.



http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2000128