{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T09:36:55Z","timestamp":1781257015317,"version":"3.54.1"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272309"],"award-info":[{"award-number":["82272309"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Outstanding Youth Fund of Shaanxi Province","award":["2024JC-JCQN-72"],"award-info":[{"award-number":["2024JC-JCQN-72"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Many positive-sense RNA viruses, including viruses from the\n                    <jats:italic>Picornaviridae<\/jats:italic>\n                    ,\n                    <jats:italic>Coronaviridae<\/jats:italic>\n                    and\n                    <jats:italic>Flaviviridae<\/jats:italic>\n                    family, exploit endoplasmic reticulum (ER)-derived membrane structures as sites of genome replication. Here we use a pooled CRISPR genetic screening strategy to identify glycosylphosphatidylinositol (GPI) anchor biosynthesis and transfer genes as host factors for echovirus 7 infection. In addition to supporting the biogenesis of CD55, which is a GPI anchor protein and an entry factor for some echoviruses, the GPI anchor synthesis machinery also supports several other enterovirus infections by enhancing viral replication and replication organelle biogenesis. Disruption of GPI anchor transfer machinery compromises ER integrity and causes ER stress. Consistent with these findings, ER-resident sensor, inositol-requiring protein 1\u03b1 (IRE1\u03b1) is activated and regulated IRE1-dependent decay of mRNA (RIDD) is detected to reduce ER stress. Interestingly, enterovirus viral RNA, but not Hepatitis C Virus RNA, is degraded during this process due to specific sequences in the Untranslated Region (UTR). This study revealed novel links between GPI anchoring, ER stress and enterovirus infection, and illuminates new host targets for antiviral therapy.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013685","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T18:25:34Z","timestamp":1763490334000},"page":"e1013685","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Disrupted glycosylphosphatidylinositol anchoring induces ER stress and restricts enterovirus infection"],"prefix":"10.1371","volume":"21","author":[{"given":"Shangrui","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingli","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Tai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3304-2683","authenticated-orcid":true,"given":"Hongliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"issue":"6","key":"ppat.1013685.ref001","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41579-018-0005-4","article-title":"The life cycle of non-polio enteroviruses and how to target it","volume":"16","author":"J Baggen","year":"2018","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"ppat.1013685.ref002","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/s41564-018-0297-1","article-title":"An upstream protein-coding region in enteroviruses modulates virus infection in gut epithelial cells","volume":"4","author":"V Lulla","year":"2019","journal-title":"Nat Microbiol"},{"issue":"1","key":"ppat.1013685.ref003","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1038\/s41467-019-12040-9","article-title":"A second open reading frame in human enterovirus determines viral replication in intestinal epithelial cells","volume":"10","author":"H Guo","year":"2019","journal-title":"Nat Commun"},{"key":"ppat.1013685.ref004","doi-asserted-by":"crossref","first-page":"4529","DOI":"10.3390\/v7082832","article-title":"Replication and inhibitors of enteroviruses and parechoviruses","volume":"7","author":"L van der Linden","year":"2015","journal-title":"Viruses-Basel"},{"key":"ppat.1013685.ref005","article-title":"Enterovirus replication organelles and inhibitors of their formation","volume":"11","author":"H Li","year":"2020","journal-title":"Frontiers in Microbiology"},{"key":"ppat.1013685.ref006","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1128\/JVI.05937-11","article-title":"Complex dynamic development of poliovirus membranous replication complexes","volume":"86","author":"GA Belov","year":"2012","journal-title":"Journal of Virology"},{"issue":"5","key":"ppat.1013685.ref007","article-title":"The transformation of enterovirus replication structures: a three-dimensional study of single- and double-membrane compartments","volume":"2","author":"RWAL Limpens","year":"2011","journal-title":"mBio"},{"issue":"3","key":"ppat.1013685.ref008","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00951-19","article-title":"Origins of Enterovirus Replication Organelles Established by Whole-Cell Electron Microscopy","volume":"10","author":"CE Melia","year":"2019","journal-title":"mBio"},{"issue":"10","key":"ppat.1013685.ref009","doi-asserted-by":"crossref","first-page":"6576","DOI":"10.1128\/jvi.70.10.6576-6588.1996","article-title":"Cellular origin and ultrastructure of membranes induced during poliovirus infection","volume":"70","author":"A Schlegel","year":"1996","journal-title":"J Virol"},{"issue":"5","key":"ppat.1013685.ref010","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.cell.2010.03.050","article-title":"Viral reorganization of the secretory pathway generates distinct organelles for RNA replication","volume":"141","author":"N-Y Hsu","year":"2010","journal-title":"Cell"},{"issue":"1","key":"ppat.1013685.ref011","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00018-015-2052-6","article-title":"The endoplasmic reticulum: structure, function and response to cellular signaling","volume":"73","author":"DS Schwarz","year":"2016","journal-title":"Cell Mol Life Sci"},{"issue":"5","key":"ppat.1013685.ref012","doi-asserted-by":"crossref","DOI":"10.1093\/femsre\/fuab016","article-title":"The endoplasmic reticulum unfolded protein response - homeostasis, cell death and evolution in virus infections","volume":"45","author":"V Prasad","year":"2021","journal-title":"FEMS Microbiol Rev"},{"issue":"1","key":"ppat.1013685.ref013","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/febs.15107","article-title":"A guide to assessing endoplasmic reticulum homeostasis and stress in mammalian systems","volume":"287","author":"D Sicari","year":"2020","journal-title":"FEBS J"},{"issue":"2","key":"ppat.1013685.ref014","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrm3270","article-title":"The unfolded protein response: controlling cell fate decisions under ER stress and beyond","volume":"13","author":"C Hetz","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"ppat.1013685.ref015","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.cell.2014.06.026","article-title":"ER stress-induced clearance of misfolded GPI-anchored proteins via the secretory pathway","volume":"158","author":"P Satpute-Krishnan","year":"2014","journal-title":"Cell"},{"issue":"5","key":"ppat.1013685.ref016","doi-asserted-by":"crossref","first-page":"855","DOI":"10.3390\/biom13050855","article-title":"(Patho)Physiology of Glycosylphosphatidylinositol-Anchored Proteins I: Localization at Plasma Membranes and Extracellular Compartments","volume":"13","author":"GA M\u00fcller","year":"2023","journal-title":"Biomolecules"},{"issue":"3","key":"ppat.1013685.ref017","doi-asserted-by":"crossref","first-page":"190290","DOI":"10.1098\/rsob.190290","article-title":"Biosynthesis and biology of mammalian GPI-anchored proteins","volume":"10","author":"T Kinoshita","year":"2020","journal-title":"Open Biol"},{"issue":"13","key":"ppat.1013685.ref018","doi-asserted-by":"crossref","first-page":"6245","DOI":"10.1073\/pnas.91.13.6245","article-title":"Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses","volume":"91","author":"JM Bergelson","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"21","key":"ppat.1013685.ref019","doi-asserted-by":"crossref","first-page":"5070","DOI":"10.1002\/j.1460-2075.1994.tb06836.x","article-title":"Decay-accelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno-focal cloning method","volume":"13","author":"T Ward","year":"1994","journal-title":"EMBO J"},{"key":"ppat.1013685.ref020","article-title":"Molecular basis of differential receptor usage for naturally occurring CD55-binding and -nonbinding coxsackievirus B3 strains","volume":"119","author":"QL Wang","year":"2022","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"7","key":"ppat.1013685.ref021","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.tim.2016.02.017","article-title":"Fat (al) attraction: Picornaviruses Usurp Lipid Transfer at Membrane Contact 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