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Significance Many bacterial pathogens infect eukaryotic cells by injecting bacterial virulence factors or effectors into the cytosol of their hosts. These effector proteins have evolved to manipulate cellular pathways and favor bacterial replication.Legionella pneumophila , the cause of Legionnaires’ disease, synthesizes &gt;300 effector proteins. Here, we screenedLegionella effectors to probe tombusvirus (TBSV)–host interactions and identify antiviral factors against TBSV in yeast surrogate host. As proof of concept that bacterial effectors can be used as tools to identify cellular pathways used by viruses, we characterized the antiviral effect of DrrA effector ofLegionella . This led to the discovery that Rab1 small GTPase, the cellular target of DrrA, and COPII vesicles are coopted by TBSV for building the viral replication compartment.

Screening Legionella effectors for antiviral effects reveals Rab1 GTPase as a proviral factor coopted for tombusvirus replication