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 ant...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-1β,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.展开更多
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).
文摘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-1β,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.
