biostudies-literatureKalugotla GNational Institute of Allergy and Infectious DiseasesNIAID NIH HHSBurroughs Wellcome FundNCI NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHSe1012900https://www.ebi.ac.uk/biostudies/studies/S-EPMC12646485biostudies-literatureUnknown21(11)Autophagy is an essential cellular process which functions to maintain homeostasis in response to stressors such as starvation or infection. Here, we report that a subset of autophagy factors including ATG-3 play an antiviral role in Orsay virus infection of Caenorhabditis elegans. Orsay virus infection does not modulate autophagic flux, and re-feeding after starvation limits Orsay virus infection and blocks autophagic flux, suggesting that the role of ATG-3 in Orsay virus susceptibility is independent of its role in maintaining autophagic flux. atg-3 mutants phenocopy rde-1 mutants, which have a defect in RNA interference (RNAi), in susceptibility to Orsay virus infection and transcriptional response to infection. However, atg-3 mutants do not exhibit defects in RNAi. Additionally, ATG-3 PLoS pathogensATG-3 limits Orsay virus infection in C. elegans and regulates collagen pathways.PMC12646485R01 AI173360P30 CA091842R35 GM152192T32 AI007163T32 GM007200Investigator in the Pathogenesis of Infectious DiseaseSchriefer LAKalugotla GPerez LCMorrison SAMarmerstein VSchedl TPak SCBaldridge MTSilverman GAWang LfalseATG-3 limits Orsay virus infection in C. elegans and regulates collagen pathways.Autophagy is an essential cellular process which functions to maintain homeostasis in response to stressors such as starvation or infection. Here, we report that a subset of autophagy factors including ATG-3 play an antiviral role in Orsay virus infection of Caenorhabditis elegans. Orsay virus infection does not modulate autophagic flux, and re-feeding after starvation limits Orsay virus infection and blocks autophagic flux, suggesting that the role of ATG-3 in Orsay virus susceptibility is independent of its role in maintaining autophagic flux. atg-3 mutants phenocopy rde-1 mutants, which have a defect in RNA interference (RNAi), in susceptibility to Orsay virus infection and transcriptional response to infection. However, atg-3 mutants do not exhibit defects in RNAi. Additionally, ATG-3 2025-01-01T00:00:00Z2025 Nov2026-05-20T03:17:16.527Z2026-05-20T03:09:34.698ZS-EPMC126464854125244610.1371/journal.ppat.1012900