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Some functions of\n                    <jats:italic>ATG<\/jats:italic>\n                    genes are independent of their role in degradative autophagy. One of the first described of these\n                    <jats:italic>ATG<\/jats:italic>\n                    gene-dependent, but degradative autophagy independent, processes is the requirement for a subset of\n                    <jats:italic>ATG<\/jats:italic>\n                    genes in interferon-\u03b3 (IFN\u03b3)-induced inhibition of norovirus and\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    replication. Herein, we identified additional genes that are required for, or that negatively regulate, this innate immune effector pathway. Enzymes in the UFMylation pathway negatively regulated IFN\u03b3-induced inhibition of norovirus replication via effects of\n                    <jats:italic>Ern1<\/jats:italic>\n                    . IFN\u03b3-induced inhibition of norovirus replication required\n                    <jats:italic>Gate-16<\/jats:italic>\n                    (also termed\n                    <jats:italic>GabarapL2<\/jats:italic>\n                    ),\n                    <jats:italic>Wipi2b<\/jats:italic>\n                    ,\n                    <jats:italic>Atg9a<\/jats:italic>\n                    ,\n                    <jats:italic>Cul3<\/jats:italic>\n                    , and\n                    <jats:italic>Klhl9<\/jats:italic>\n                    but not\n                    <jats:italic>Becn1<\/jats:italic>\n                    (encoding Beclin 1),\n                    <jats:italic>Atg14<\/jats:italic>\n                    ,\n                    <jats:italic>Uvrag<\/jats:italic>\n                    , or\n                    <jats:italic>Sqstm1<\/jats:italic>\n                    . The phosphatidylinositol-3-phosphate and ATG16L1-binding domains of WIPI2B, as well as the ATG5-binding domain of ATG16L1, were required for IFN\u03b3-induced inhibition of norovirus replication. Other members of the\n                    <jats:italic>Cul3<\/jats:italic>\n                    ,\n                    <jats:italic>Atg8<\/jats:italic>\n                    , and\n                    <jats:italic>Wipi2<\/jats:italic>\n                    gene families were not required, demonstrating exquisite specificity within these gene families for participation in IFN\u03b3 action. The generality of some aspects of this mechanism was demonstrated by a role for GATE-16 and WIPI2 in IFN\u03b3-induced control of\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    infection in human cells. These studies further delineate the genes and mechanisms of an\n                    <jats:italic>ATG<\/jats:italic>\n                    gene-dependent programmable form of cytokine-induced innate intracellular immunity.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Interferon-\u03b3 (IFN\u03b3) is a critical mediator of cell-intrinsic immunity to intracellular pathogens. Understanding the complex cellular mechanisms supporting robust interferon-\u03b3-induced host defenses could aid in developing new therapeutics to treat infections. Here, we examined the impact of autophagy genes in the interferon-\u03b3-induced host response. We demonstrate that genes within the autophagy pathway including\n                      <jats:italic>Wipi2<\/jats:italic>\n                      ,\n                      <jats:italic>Atg9<\/jats:italic>\n                      , and\n                      <jats:italic>Gate-16<\/jats:italic>\n                      , as well as ubiquitin ligase complex genes\n                      <jats:italic>Cul3<\/jats:italic>\n                      and\n                      <jats:italic>Klhl9<\/jats:italic>\n                      are required for IFN\u03b3-induced inhibition of murine norovirus (norovirus hereinafter) replication in mouse cells.\n                      <jats:italic>WIPI2<\/jats:italic>\n                      and\n                      <jats:italic>GATE-16<\/jats:italic>\n                      were also required for IFN\u03b3-mediated restriction of parasite growth within the\n                      <jats:italic>Toxoplasma gondii<\/jats:italic>\n                      parasitophorous vacuole in human cells. Furthermore, we found that perturbation of UFMylation pathway components led to more robust IFN\u03b3-induced inhibition of norovirus via regulation of endoplasmic reticulum (ER) stress. Enhancing or inhibiting these dynamic cellular components could serve as a strategy to control intracellular pathogens and maintain an effective immune response.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02332-23","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T09:02:17Z","timestamp":1698742937000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Autophagy gene-dependent intracellular immunity triggered by interferon-\u03b3"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-7290","authenticated-orcid":false,"given":"Michael R.","family":"McAllaster","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"},{"name":"Vir Biotechnology, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya","family":"Bhushan","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale R.","family":"Balce","sequence":"additional","affiliation":[{"name":"Vir Biotechnology, San Francisco, California, USA"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-9200","authenticated-orcid":true,"given":"Anthony","family":"Orvedahl","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA"},{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8916-2230","authenticated-orcid":true,"given":"Arnold","family":"Park","sequence":"additional","affiliation":[{"name":"Vir Biotechnology, San Francisco, California, USA"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0846-5462","authenticated-orcid":true,"given":"Seungmin","family":"Hwang","sequence":"additional","affiliation":[{"name":"Vir Biotechnology, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meagan E.","family":"Sullender","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences &amp; Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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