The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm

作     者：Matthias Hamdorf Thomas Imhof Ben Bailey-Elkin Janina Betz Sebastian JTheobald Alexander Simonis Veronica Di Cristanziano Lutz Gieselmann Felix Dewald Clara Lehmann Max Augustin Florian Klein Miguel AAlejandre Alcazar Robert Rongisch Mario Fabri Jan Rybniker Heike Goebel Jörg Stetefeld Bent Brachvogel Claus Cursiefen Manuel Koch Felix Bock Matthias Hamdorf;Thomas Imhof;Ben Bailey-Elkin;Janina Betz;Sebastian J.Theobald;Alexander Simonis;Veronica Di Cristanziano;Lutz Gieselmann;Felix Dewald;Clara Lehmann;Max Augustin;Florian Klein;Miguel A.Alejandre Alcazar;Robert Rongisch;Mario Fabri;Jan Rybniker;Heike Goebel;Jörg Stetefeld;Bent Brachvogel;Claus Cursiefen;Manuel Koch;Felix Bock

作者机构：Cornea Lab Experimental OphthalmologyDepartment of OphthalmologyFaculty of Medicine and University Hospital Cologne50937 CologneGermany Terasaki Institute for Biomedical InnovationLos AngelesCA 90024USA Center for BiochemistryFaculty of Medicine and University Hospital Cologne50931 CologneGermany Institute for Experimental Dentistry and Oral Musculoskeletal BiologyFaculty of Medicine and University Hospital Cologne50931 CologneGermany Department of MicrobiologyUniversity of ManitobaWinnipeg MB R3B 2E9 ManitobaCanada Department I of Internal MedicineDivision of Infectious DiseasesFaculty of Medicine and University Hospital Cologne50937 CologneGermany Center for Molecular Medicine CologneUniversity of Cologne50931 CologneGermany Institute of VirologyFaculty of Medicine and University Hospital Cologne50935 CologneGermany German Center for Infection Research(DZIF)Partner Site Bonn-Cologne50931 CologneGermany Department of Children and Adolescent MedicineFaculty of Medicine and University Hospital Cologne50931 CologneGermany Cologne Excellence Cluster Stress Responses in Aging-associated Diseases50931 CologneGermany Institute for Lung Health(ILH)Universities of Gießen and Marburg Lung CentreMember of the German Center for Lung Research35392 GießenGermany DermatologyFaculty of Medicine and University Hospital Cologne50937 CologneGermany Institute of PathologyFaculty of Medicine and University Hospital Cologne50937 CologneGermany Department of Pediatrics and Adolescent MedicineExperimental NeonatologyFaculty of Medicine and University Hospital Cologne50931 CologneGermany 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2023年第15卷第10期

页      面：39-53页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：supported by the German Research Foundation(DFG)research unit FOR2240(www.FOR2240.de)BO4489/1-1,BO4489/1-2,BO4489/3-1(F.B.)Cu 47/9-1 and 12-1,the Center for Molecular Medicine Cologne(CMMC)(F.B.,C.C.,and M.K.) the German Research Foundation(DFG)research unit FOR2722(M.K.and B.B.) J.S.is a Tier-1 Canada Research Chair and received additional support from the Canadian Institute of Health Research(CIHR-PJTÑ52935 and 178097) 

主　　题：COVID-19 SARS-CoV-2 ORF8 cytokine storm dendritic cells 

摘      要：The novel coronavirus pandemic,first reported in December 2019,was caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells,which can elicit acute respiratory distress syndrome(ARDS)characterized by the rapid onset of widespread inflammation,the so-called cytokine *** response to viral infections,monocytes are recruited into the lung and subsequently differentiate into dendritic cells(DCs).DCs are critical players in the development of acute lung inflammation that causes ***,we focus on the interaction of a specific SARS-CoV-2 open reading frame protein,ORF8,with *** show that ORF8 binds to DCs,causes pre-maturation of differentiating DCs,and induces the secretion of multiple proinflammatory cytokines by these *** addition,we identified DC-SIGN as a possible interaction partner of ORF8 on *** of ORF8 leads to reduced production of IL-1β,IL-6,IL-12p70,TNF-α,MCP-1(also named CCL2),and IL-10 by ***,a neutralizing antibody blocking the ORF8-mediated cytokine and chemokine response could be an improved therapeutic strategy against SARS-CoV-2.