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

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Journal of Molecular Cell Biology 2023年第10期15卷 39-53页

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 Cornea Lab Experimental Ophthalmology Department of OphthalmologyFaculty of Medicine and University Hospital Cologne50937 CologneGermany Terasaki Institute for Biomedical Innovation Los AngelesCA 90024USA Center for Biochemistry Faculty of Medicine and University Hospital Cologne50931 CologneGermany Institute for Experimental Dentistry and Oral Musculoskeletal Biology Faculty of Medicine and University Hospital Cologne50931 CologneGermany Department of Microbiology University of ManitobaWinnipeg MB R3B 2E9 ManitobaCanada Department I of Internal Medicine Division of Infectious DiseasesFaculty of Medicine and University Hospital Cologne50937 CologneGermany Center for Molecular Medicine Cologne University of Cologne50931 CologneGermany Institute of Virology Faculty of Medicine and University Hospital Cologne50935 CologneGermany German Center for Infection Research(DZIF) Partner Site Bonn-Cologne50931 CologneGermany Department of Children and Adolescent Medicine Faculty of Medicine and University Hospital Cologne50931 CologneGermany Cologne Excellence Cluster Stress Responses in Aging-associated Diseases 50931 CologneGermany Institute for Lung Health(ILH) Universities of Gießen and Marburg Lung CentreMember of the German Center for Lung Research35392 GießenGermany Dermatology Faculty of Medicine and University Hospital Cologne50937 CologneGermany Institute of Pathology Faculty of Medicine and University Hospital Cologne50937 CologneGermany Department of Pediatrics and Adolescent Medicine Experimental NeonatologyFaculty of Medicine and University Hospital Cologne50931 CologneGermany

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.

关键词： COVID-19 SARS-CoV-2 ORF8 cytokine storm dendritic cells

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