The Dietary Restriction-Like Gene drl-1 , Which Encodes a Putative Serine/Threonine Kinase, Is Essential for Orsay Virus Infection in Caenorhabditis elegans

Orsay virus is the only known natural virus pathogen of , and its discovery has enabled virus-host interaction studies in this model organism. Host genes required for viral infection remain understudied. We previously established a forward genetic screen based on a virus-inducible green fluorescent protein transcriptional reporter to identify novel host factors essential for virus infection. Here, we report the essential role in Orsay virus infection of the dietary restriction-like ( ) gene, which encodes a serine/threonine kinase similar to the mammalian MEKK3 kinase. Ablation of led to a >10,000-fold reduction in Orsay virus RNA levels, which could be rescued by ectopic expression of DRL-1. DRL-1 was dispensable for Orsay replication from an endogenous transgene replicon, suggesting that DRL-1 affects a prereplication stage of the Orsay life cycle. Thus, this study demonstrates the power of as a model to identify novel virus-host interactions essential for virus infection. The recent discovery of Orsay virus, the only known natural virus of , provides a unique opportunity to study virus-host interactions that mediate infection in a genetically tractable multicellular model organism. As viruses remain a global threat to human health, better insights into cellular components that enable virus infection and replication can ultimately lead to the development of new targets for antiviral therapeutics.