The Glycolytic Pyruvate Kinase Is Recruited Directly into the Viral Replicase Complex to Generate ATP for RNA Synthesis

Abstract

Viruses accomplish their replication by exploiting many cellular resources, including metabolites and energy. Similarly to other (+)RNA viruses, tomato bushy stunt virus (TBSV) induces major changes in infected cells. However, the source of energy required to fuel TBSV replication is unknown. We find that TBSV co-opts the cellular glycolytic ATP-generating pyruvate kinase (PK) directly into the viral replicase complex to boost progeny RNA synthesis. The co-opted PK generates high levels of ATP within the viral replication compartment at the expense of a reduction in cytosolic ATP pools. The ATP generated by the co-opted PK is used to promote the helicase activity of recruited cellular DEAD-box helicases, which are involved in the production of excess viral (+)RNA progeny. Altogether, recruitment of PK and local production of ATP within the replication compartment allow the virus replication machinery an access to plentiful ATP, facilitating robust virus replication.