Abstract
The intricate interactions between viruses and hosts include exploitation of host cells for viral replication by using many cellular resources, metabolites and energy. Tomato bushy stunt virus (TBSV), similar to other (+)RNA viruses, induces major changes in infected cells that lead to the formation of large replication compartments consisting of aggregated peroxisomal and ER membranes. Yet, it is not known how TBSV obtains the energy to fuel these energy-consuming processes. In the current work, the authors discovered that TBSV co-opts the glycolytic ATP-generating Pgk1 phosphoglycerate kinase to facilitate the assembly of new viral replicase complexes. The recruitment of Pgk1 into the viral replication compartment is through direct interaction with the viral replication proteins. Altogether, we provide evidence that the ATP generated locally within the replication compartment by the co-opted Pgk1 is used to fuel the ATP-requirement of the co-opted heat shock protein 70 (Hsp70) chaperone, which is essential for the assembly of new viral replicase complexes and the activation of functional viral RNA-dependent RNA polymerase. The advantage of direct recruitment of Pgk1 into the virus replication compartment could be that the virus replicase assembly does not need to intensively compete with cellular processes for access to ATP. In addition, local production of ATP within the replication compartment could greatly facilitate the efficiency of Hsp70-driven replicase assembly by providing high ATP concentration within the replication compartment.
Highlights
Positive-strand (+)RNA viruses build robust viral replication machineries, called replication organelles, with the help of many co-opted cellular factors
Positive-strand (+)RNA viruses build replication organelles with the help of many coopted cellular factors and by usurping cellular metabolites and energy, which frequently lead to disease states in plants, animals and humans
The authors discovered that tomato bushy stunt virus (TBSV) co-opts the glycolytic ATP-generating Pgk1 phosphoglycerate kinase to facilitate the intracellular assembly of new viral replicase complexes
Summary
Positive-strand (+)RNA viruses build robust viral replication machineries, called replication organelles, with the help of many co-opted cellular factors. Overall, (+)RNA viruses induce major metabolic and structural changes in the infected cells, which frequently lead to disease states [1,2,3,4,5]. The replication compartments contain numerous vesicle-like structures in the limiting membrane of peroxisomes, which harbor the viral replicase [6,7,8]. TBSV co-opts numerous host proteins to support various viral functions, including the heat shock protein 70 (Hsp70), the endosomal sorting complex required for transport (ESCRT) machinery, translation factors and DEAD-box RNA helicases [11,12,13,14,15,16,17]. TBSV-induced major changes in the cell require energy, but how TBSV can obtain the energy to fuel these energy-demanding processes is not known
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