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

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

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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 storm.In 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 ARDS.Here,we focus on the interaction of a specific SARS-CoV-2 open reading frame protein,ORF8,with DCs.We show that ORF8 binds to DCs,causes pre-maturation of differentiating DCs,and induces the secretion of multiple proinflammatory cytokines by these cells.In addition,we identified DC-SIGN as a possible interaction partner of ORF8 on DCs.Blockade of ORF8 leads to reduced production of IL-1 β,IL-6,IL-12p70,TNF-α,MCP-1(also named CCL2),and IL-10 by DCs.Therefore,a neutralizing antibody blocking the ORF8-mediated cytokine and chemokine response could be an improved therapeutic strategy against SARS-CoV-2.

COVID-19SARS-CoV-2ORF8cytokine stormdendritic cells

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、J?rg Stetefeld、Bent Brachvogel、Claus Cursiefen、Manuel Koch、Felix Bock

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Cornea Lab Experimental Ophthalmology,Department of Ophthalmology,Faculty of Medicine and University Hospital Cologne,50937 Cologne,Germany

Terasaki Institute for Biomedical Innovation,Los Angeles,CA 90024,USA

Center for Biochemistry,Faculty of Medicine and University Hospital Cologne,50931 Cologne,Germany

Institute for Experimental Dentistry and Oral Musculoskeletal Biology,Faculty of Medicine and University Hospital Cologne,50931 Cologne,Germany

Department of Microbiology,University of Manitoba,Winnipeg MB R3B 2E9 Manitoba,Canada

Department I of Internal Medicine,Division of Infectious Diseases,Faculty of Medicine and University Hospital Cologne,50937 Cologne,Germany

Center for Molecular Medicine Cologne,University of Cologne,50931 Cologne,Germany

Institute of Virology,Faculty of Medicine and University Hospital Cologne,50935 Cologne,Germany

German Center for Infection Research(DZIF),Partner Site Bonn-Cologne,50931 Cologne,Germany

Department of Children and Adolescent Medicine,Faculty of Medicine and University Hospital Cologne,50931 Cologne,Germany

Cologne Excellence Cluster Stress Responses in Aging-associated Diseases,50931 Cologne,Germany

Institute for Lung Health(ILH),Universities of Gießen and Marburg Lung Centre,Member of the German Center for Lung Research,35392 Gießen,Germany

Dermatology,Faculty of Medicine and University Hospital Cologne,50937 Cologne,Germany

Institute of Pathology,Faculty of Medicine and University Hospital Cologne,50937 Cologne,Germany

Department of Pediatrics and Adolescent Medicine,Experimental Neonatology,Faculty of Medicine and University Hospital Cologne,50931 Cologne,Germany

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German Research Foundation(DFG)research unit FOR2240German Research Foundation(DFG)research unit FOR2240German Research Foundation(DFG)research unit FOR2240German Research Foundation(DFG)research unit FOR2240Center for Molecular Medicine Cologne(CMMC)German Research Foundation(DFG)research unit FOR2722Canadian Institute of HealthCanadian Institute of Health

BO4489/1-1BO4489/1-2BO4489/3-1F.B.Cu 47/9-112-1CIHR-PJT?52935178097

2023

10.1093/jmcb/mjad062

分子细胞生物学报(英文版)
中国科学院上海生命科学研究院,生物化学与细胞生物学研究所,中国细胞生物学学会

分子细胞生物学报(英文版)

CSTPCDCSCD
影响因子：0.595
ISSN：1673-520X
年,卷(期)：2023.(10)
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