{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:37:56Z","timestamp":1792802276291,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011128","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China, SGC's Rapid Response Funding for COVID-19","award":["C-0002"],"award-info":[{"award-number":["C-0002"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970008"],"award-info":[{"award-number":["81970008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000020"],"award-info":[{"award-number":["82000020"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31702205"],"award-info":[{"award-number":["31702205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2019CDYGZD009"],"award-info":[{"award-number":["2019CDYGZD009"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2020CDJYGRH-1005"],"award-info":[{"award-number":["2020CDJYGRH-1005"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Chongqing, China","award":["cstc2020jcyj-msxmX0460"],"award-info":[{"award-number":["cstc2020jcyj-msxmX0460"]}]},{"name":"Natural Science Foundation of Chongqing, China","award":["cstc2020jcyj-bshX0105"],"award-info":[{"award-number":["cstc2020jcyj-bshX0105"]}]},{"name":"Chongqing Talents: Exceptional Young Talents Project","award":["cstc2021ycjh-bgzxm0099"],"award-info":[{"award-number":["cstc2021ycjh-bgzxm0099"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Coronavirus disease 2019 is a respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence on the pathogenesis of SARS-CoV-2 is accumulating rapidly. In addition to structural proteins such as Spike and Envelope, the functional roles of non-structural and accessory proteins in regulating viral life cycle and host immune responses remain to be understood. Here, we show that open reading frame 8 (ORF8) acts as messenger for inter-cellular communication between alveolar epithelial cells and macrophages during SARS-CoV-2 infection. Mechanistically, ORF8 is a secretory protein that can be secreted by infected epithelial cells via both conventional and unconventional secretory pathways. Conventionally secreted ORF8 is glycosylated and loses the ability to recognize interleukin 17 receptor A of macrophages, possibly due to the steric hindrance imposed by N-glycosylation at Asn78. However, unconventionally secreted ORF8 does not undergo glycosylation without experiencing the ER-Golgi trafficking, thereby activating the downstream NF-\u03baB signaling pathway and facilitating a burst of cytokine release. Furthermore, we show that ORF8 deletion in SARS-CoV-2 attenuates inflammation and yields less lung lesions in hamsters. Our data collectively highlights a role of ORF8 protein in the development of cytokine storms during SARS-CoV-2 infection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011128","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T13:41:44Z","timestamp":1674481304000},"page":"e1011128","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":32,"title":["Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection"],"prefix":"10.1371","volume":"19","author":[{"given":"Xiaoyuan","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Zaky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Pavani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusan","family":"Kunec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Trimpert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5961-2947","authenticated-orcid":true,"given":"Haibo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"issue":"1","key":"ppat.1011128.ref001","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41392-021-00679-0","article-title":"The signal pathways and treatment of cytokine storm in COVID-19.","volume":"6","author":"L Yang","year":"2021","journal-title":"Signal Transduct Target Ther."},{"issue":"10223","key":"ppat.1011128.ref002","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan","volume":"395","author":"C Huang","year":"2020","journal-title":"China. Lancet"},{"issue":"5","key":"ppat.1011128.ref003","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1097\/SHK.0000000000001769","article-title":"Cytokine Drizzle-The Rationale for Abandoning \"Cytokine Storm\".","volume":"56","author":"AE Stolarski","year":"2021","journal-title":"Shock"},{"issue":"17","key":"ppat.1011128.ref004","article-title":"Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections.","volume":"5","author":"KE Remy","year":"2020","journal-title":"JCI Insight."},{"issue":"6","key":"ppat.1011128.ref005","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1093\/nsr\/nwaa036","article-title":"On the origin and continuing evolution of SARS-CoV-2.","volume":"7","author":"X Tang","year":"2020","journal-title":"Natl Sci Rev."},{"issue":"1","key":"ppat.1011128.ref006","doi-asserted-by":"crossref","first-page":"15177","DOI":"10.1038\/s41598-018-33487-8","article-title":"Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission.","volume":"8","author":"D Muth","year":"2018","journal-title":"Sci Rep."},{"issue":"10251","key":"ppat.1011128.ref007","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0140-6736(20)31757-8","article-title":"Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study","volume":"396","author":"BE Young","year":"2020","journal-title":"Lancet"},{"issue":"4","key":"ppat.1011128.ref008","doi-asserted-by":"crossref","first-page":"102293","DOI":"10.1016\/j.isci.2021.102293","article-title":"ORF8 contributes to cytokine storm during SARS-CoV-2 infection by activating IL-17 pathway.","volume":"24","author":"X Lin","year":"2021","journal-title":"iScience."},{"issue":"19","key":"ppat.1011128.ref009","doi-asserted-by":"crossref","first-page":"10705","DOI":"10.3390\/ijms221910705","article-title":"Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes.","volume":"22","author":"P Bhadra","year":"2021","journal-title":"Int J Mol Sci."},{"issue":"12","key":"ppat.1011128.ref010","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.tcb.2019.08.007","article-title":"ER-to-Golgi Transport: A Sizeable Problem","volume":"29","author":"J McCaughey","year":"2019","journal-title":"Trends in cell biology"},{"key":"ppat.1011128.ref011","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3389\/fimmu.2014.00538","article-title":"Cytokine Secretion in Macrophages: SNAREs, Rabs, and Membrane Trafficking.","volume":"5","author":"RZ Murray","year":"2014","journal-title":"Front Immunol."},{"issue":"12","key":"ppat.1011128.ref012","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1038\/emboj.2013.104","article-title":"Unconventional protein secretion: an evolving mechanism","volume":"32","author":"V. Malhotra","year":"2013","journal-title":"The EMBO journal"},{"key":"ppat.1011128.ref013","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.semcdb.2018.02.010","article-title":"A direct gateway into the extracellular space: Unconventional secretion of FGF2 through self-sustained plasma membrane pores","volume":"83","author":"JP Steringer","year":"2018","journal-title":"Seminars in cell & developmental biology"},{"issue":"1","key":"ppat.1011128.ref014","doi-asserted-by":"crossref","first-page":"e02344","DOI":"10.1128\/mBio.02344-17","article-title":"Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses.","volume":"9","author":"RP McNamara","year":"2018","journal-title":"mBio"},{"issue":"7","key":"ppat.1011128.ref015","doi-asserted-by":"crossref","first-page":"e1007907","DOI":"10.1371\/journal.ppat.1007907","article-title":"Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells.","volume":"15","author":"N Mukhamedova","year":"2019","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1011128.ref016","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41419-020-03314-y","article-title":"Structure, function, and pathology of protein O-glucosyltransferases.","volume":"12","author":"MZ Mehboob","year":"2021","journal-title":"Cell Death Dis."},{"issue":"7","key":"ppat.1011128.ref017","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/nrm3383","article-title":"Vertebrate protein glycosylation: diversity, synthesis and function","volume":"13","author":"KW Moremen","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"12","key":"ppat.1011128.ref018","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/s41580-020-00294-x","article-title":"Global view of human protein glycosylation pathways and functions","volume":"21","author":"KT Schjoldager","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"11","key":"ppat.1011128.ref019","doi-asserted-by":"crossref","first-page":"e49224","DOI":"10.1371\/journal.pone.0049224","article-title":"The evolutionary pattern of glycosylation sites in influenza virus (H5N1) hemagglutinin and neuraminidase.","volume":"7","author":"W Chen","year":"2012","journal-title":"PLoS One"},{"key":"ppat.1011128.ref020","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.3389\/fmicb.2017.01415","article-title":"Dengue Virus Glycosylation: What Do We Know?","volume":"8","author":"SSL Yap","year":"2017","journal-title":"Front Microbiol."},{"key":"ppat.1011128.ref021","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.sbi.2017.03.008","article-title":"Structural principles controlling HIV envelope glycosylation","volume":"44","author":"AJ Behrens","year":"2017","journal-title":"Curr Opin Struct Biol"},{"issue":"11","key":"ppat.1011128.ref022","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00104-20","article-title":"Flavivirus Envelope Protein Glycosylation: Impacts on Viral Infection and Pathogenesis","volume":"94","author":"DL Carbaugh","year":"2020","journal-title":"Journal of virology"},{"issue":"10","key":"ppat.1011128.ref023","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/s41422-021-00545-2","article-title":"O-glycosylation pattern of the SARS-CoV-2 spike protein reveals an \"O-Follow-N\" rule.","volume":"31","author":"W Tian","year":"2021","journal-title":"Cell research"},{"issue":"5","key":"ppat.1011128.ref024","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.cell.2020.07.012","article-title":"The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity","volume":"182","author":"Q Li","year":"2020","journal-title":"Cell"},{"issue":"6501","key":"ppat.1011128.ref025","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1126\/science.abb9983","article-title":"Site-specific glycan analysis of the SARS-CoV-2 spike","volume":"369","author":"Y Watanabe","year":"2020","journal-title":"Science"},{"issue":"12","key":"ppat.1011128.ref026","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1016\/j.chom.2021.11.005","article-title":"Nucleocapsid mutations R203K\/G204R increase the infectivity, fitness, and virulence of SARS-CoV-2","volume":"29","author":"H Wu","year":"2021","journal-title":"Cell Host Microbe"},{"issue":"7852","key":"ppat.1011128.ref027","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41586-020-2895-3","article-title":"Spike mutation D614G alters SARS-CoV-2 fitness","volume":"592","author":"JA Plante","year":"2021","journal-title":"Nature"},{"issue":"5","key":"ppat.1011128.ref028","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.chom.2020.04.004","article-title":"An Infectious cDNA Clone of SARS-CoV-2","volume":"27","author":"X Xie","year":"2020","journal-title":"Cell Host Microbe"},{"issue":"3","key":"ppat.1011128.ref029","doi-asserted-by":"crossref","first-page":"273","DOI":"10.4062\/biomolther.2020.226","article-title":"Differential Signaling and Virus Production in Calu-3 Cells and Vero Cells upon SARS-CoV-2 Infection.","volume":"29","author":"BK Park","year":"2021","journal-title":"Biomol Ther (Seoul)."},{"issue":"2","key":"ppat.1011128.ref030","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3390\/v14020441","article-title":"Naive Human Macrophages Are Refractory to SARS-CoV-2 Infection and Exhibit a Modest Inflammatory Response Early in Infection.","volume":"14","author":"Z Zhang","year":"2022","journal-title":"Viruses"},{"issue":"3","key":"ppat.1011128.ref031","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1093\/infdis\/jiab044","article-title":"Monocytes and Macrophages, Targets of Severe Acute Respiratory Syndrome Coronavirus 2: The Clue for Coronavirus Disease 2019 Immunoparalysis","volume":"224","author":"A Boumaza","year":"2021","journal-title":"J Infect Dis"},{"key":"ppat.1011128.ref032","doi-asserted-by":"crossref","first-page":"741502","DOI":"10.3389\/fimmu.2021.741502","article-title":"Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions.","volume":"12","author":"MM Abdelmoaty","year":"2021","journal-title":"Frontiers in immunology"},{"issue":"7838","key":"ppat.1011128.ref033","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/s41586-020-2665-2","article-title":"Structures and distributions of SARS-CoV-2 spike proteins on intact virions","volume":"588","author":"Z Ke","year":"2020","journal-title":"Nature"},{"issue":"2","key":"ppat.1011128.ref034","doi-asserted-by":"crossref","first-page":"e0040222","DOI":"10.1128\/mbio.00402-22","article-title":"Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8.","volume":"13","author":"X Wu","year":"2022","journal-title":"mBio"},{"issue":"21","key":"ppat.1011128.ref035","doi-asserted-by":"crossref","first-page":"12060","DOI":"10.3390\/ijms222112060","article-title":"Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Promoted Osteogenesis by Increasing Vesicle Trafficking, Wnt\/Ca(2+), and BMP\/Smad Signaling","volume":"22","author":"S Lin","year":"2021","journal-title":"Int J Mol Sci"},{"key":"ppat.1011128.ref036","doi-asserted-by":"crossref","first-page":"101296","DOI":"10.1016\/j.molmet.2021.101296","article-title":"Receptor Activity-Modifying Protein 2 (RAMP2) alters glucagon receptor trafficking in hepatocytes with functional effects on receptor signalling.","volume":"53","author":"ER McGlone","year":"2021","journal-title":"Mol Metab."},{"key":"ppat.1011128.ref037","article-title":"The ER-Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis.","volume":"2","author":"L Ge","year":"2013","journal-title":"Elife"},{"issue":"12","key":"ppat.1011128.ref038","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.tibs.2020.08.001","article-title":"Nonredundant Roles of GRASP55 and GRASP65 in the Golgi Apparatus and Beyond","volume":"45","author":"X Zhang","year":"2020","journal-title":"Trends in biochemical sciences"},{"issue":"1","key":"ppat.1011128.ref039","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1038\/s41467-021-22618-x","article-title":"FUT8-mediated aberrant N-glycosylation of B7H3 suppresses the immune response in triple-negative breast cancer","volume":"12","author":"Y Huang","year":"2021","journal-title":"Nature communications"},{"issue":"4","key":"ppat.1011128.ref040","doi-asserted-by":"crossref","first-page":"101227","DOI":"10.1016\/j.jbc.2021.101227","article-title":"Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization","volume":"297","author":"CE Martin","year":"2021","journal-title":"The Journal of biological chemistry"},{"issue":"2","key":"ppat.1011128.ref041","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1002\/hep.32178","article-title":"Endoplasmic reticulum stress promotes HBV production by enhancing utilization of the autophagosome- multivesicular body axis","volume":"75","author":"X Wang","year":"2022","journal-title":"Hepatology"},{"issue":"6489","key":"ppat.1011128.ref042","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.abb3405","article-title":"Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved alpha-ketoamide inhibitors","volume":"368","author":"L Zhang","year":"2020","journal-title":"Science"},{"issue":"23","key":"ppat.1011128.ref043","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1016\/j.devcel.2021.10.006","article-title":"ORF3a of SARS-CoV-2 promotes lysosomal exocytosis-mediated viral egress","volume":"56","author":"D Chen","year":"2021","journal-title":"Dev Cell"},{"issue":"8","key":"ppat.1011128.ref044","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/s41423-020-0485-9","article-title":"The ORF3a protein of SARS-CoV-2 induces apoptosis in cells","volume":"17","author":"Y Ren","year":"2020","journal-title":"Cellular & molecular immunology"},{"issue":"13","key":"ppat.1011128.ref045","doi-asserted-by":"crossref","first-page":"108916","DOI":"10.1016\/j.celrep.2021.108916","article-title":"Sarbecovirus ORF6 proteins hamper induction of interferon signaling","volume":"34","author":"I Kimura","year":"2021","journal-title":"Cell Rep"},{"issue":"10","key":"ppat.1011128.ref046","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1038\/s41590-020-0773-7","article-title":"ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection","volume":"21","author":"A Hachim","year":"2020","journal-title":"Nat Immunol"},{"issue":"7","key":"ppat.1011128.ref047","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.cell.2020.05.015","article-title":"Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals","volume":"181","author":"A Grifoni","year":"2020","journal-title":"Cell"},{"issue":"23","key":"ppat.1011128.ref048","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2024202118","article-title":"The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Iota","volume":"118","author":"Y Zhang","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"ppat.1011128.ref049","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S1473-3099(20)30196-1","article-title":"Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study","volume":"20","author":"KK To","year":"2020","journal-title":"Lancet Infect Dis"},{"issue":"6","key":"ppat.1011128.ref050","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S1473-3099(20)30200-0","article-title":"Clinical and virological data of the first cases of COVID-19 in Europe: a case series","volume":"20","author":"FX Lescure","year":"2020","journal-title":"Lancet Infect Dis"},{"issue":"2","key":"ppat.1011128.ref051","doi-asserted-by":"crossref","first-page":"e2021785118","DOI":"10.1073\/pnas.2021785118","article-title":"Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein","volume":"118","author":"TG Flower","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"ppat.1011128.ref052","doi-asserted-by":"crossref","first-page":"101724","DOI":"10.1016\/j.jbc.2022.101724","article-title":"SARS-CoV-2 accessory protein ORF8 is secreted extracellularly as a glycoprotein homodimer","volume":"298","author":"K Matsuoka","year":"2022","journal-title":"The Journal of biological chemistry"},{"key":"ppat.1011128.ref053","article-title":"Secreted ORF8 is a pathogenic cause of severe COVID-19 and is potentially targetable with select NLRP3 inhibitors.","author":"X Wu","year":"2022","journal-title":"bioRxiv: the preprint server for biology"},{"key":"ppat.1011128.ref054","first-page":"2021","article-title":"Secreted SARS-CoV-2 ORF8 modulates the cytokine expression profile of human macrophages.","author":"N Kriplani","year":"2021","journal-title":"bioRxiv: the preprint server for biology"},{"key":"ppat.1011128.ref055","first-page":"2022","article-title":"SARS-CoV-2 ORF8 is a viral cytokine regulating immune responses.","author":"M Kohyama","year":"2022","journal-title":"bioRxiv: the preprint server for biology"},{"issue":"5","key":"ppat.1011128.ref056","doi-asserted-by":"crossref","first-page":"e02431","DOI":"10.1128\/mBio.02431-20","article-title":"Accurate Diagnosis of COVID-19 by a Novel Immunogenic Secreted SARS-CoV-2 orf8 Protein.","volume":"11","author":"X Wang","year":"2020","journal-title":"mBio"},{"key":"ppat.1011128.ref057","doi-asserted-by":"crossref","first-page":"683800","DOI":"10.3389\/fimmu.2021.683800","article-title":"SARS-CoV-2\/ACE2 Interaction Suppresses IRAK-M Expression and Promotes Pro-Inflammatory Cytokine Production in Macrophages.","volume":"12","author":"I Pantazi","year":"2021","journal-title":"Front Immunol"},{"issue":"4","key":"ppat.1011128.ref058","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1165\/ajrcmb.14.4.8600933","article-title":"Isolation and primary culture of murine alveolar type II cells","volume":"14","author":"M Corti","year":"1996","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"6","key":"ppat.1011128.ref059","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1164\/rccm.200812-1837OC","article-title":"Macrophage tumor necrosis factor-alpha induces epithelial expression of granulocyte-macrophage colony-stimulating factor: impact on alveolar epithelial repair","volume":"180","author":"L Cakarova","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"issue":"49","key":"ppat.1011128.ref060","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abk0172","article-title":"Live attenuated virus vaccine protects against SARS-CoV-2 variants of concern B.1.1.7 (Alpha) and B.1.351 (Beta).","volume":"7","author":"J Trimpert","year":"2021","journal-title":"Sci Adv."},{"issue":"9","key":"ppat.1011128.ref061","doi-asserted-by":"crossref","first-page":"e52252","DOI":"10.15252\/embr.202052252","article-title":"MiR-342 controls Mycobacterium tuberculosis susceptibility by modulating inflammation and cell death","volume":"22","author":"B Fu","year":"2021","journal-title":"EMBO Rep"},{"key":"ppat.1011128.ref062","first-page":"100058","article-title":"Site-specific N-glycosylation Characterization of Recombinant SARS-CoV-2 Spike Proteins","author":"Y Zhang","year":"2020","journal-title":"Mol Cell Proteomics"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1011128","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T02:37:07Z","timestamp":1701743827000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011128"}},"subtitle":[],"editor":[{"given":"Stanley","family":"Perlman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,1,23]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011128","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.12.03.471057","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,23]]}}}