SARS-CoV-2 ORF8 as a modulator of cytokine induction : evidence and search for molecular mechanisms
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Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction of pro-inflammatory cytokines, resulting in lung damage, cardiovascular symptoms, hematologic symptoms, acute kidney injury and multiple organ failure that can lead to death. This remarkable increase in cytokines and other inflammatory molecules is primarily caused by viral proteins, and particular interest has been given to ORF8, a unique accessory protein specific to SARS-CoV-2. Despite plenty of research, the precise mechanisms by which ORF8 induces proinflammatory cytokines are not clear. Our investigations demonstrated that ORF8 augments production of IL-6 induced by Poly(I:C) in human embryonic kidney (HEK)-293 and monocyte-derived dendritic cells (mono-DCs). We discuss our findings and the multifaceted roles of ORF8 as a modulator of cytokine response, focusing on type I interferon and IL-6, a key component of the immune response to SARS-CoV-2. In addition, we explore the hypothesis that ORF8 may act through pattern recognition receptors of dsRNA such as TLRs.
Móvio , M I , Carneiro , G , Lopes Martines , I D G , Barros de Lima , G , Sasaki , S D , Kihara , A H , Poole , E , Nevels , M M & Carlan de Silva , M C 2024 , ' SARS-CoV-2 ORF8 as a modulator of cytokine induction : evidence and search for molecular mechanisms ' , Viruses , vol. 16 , no. 1 , 161 . https://doi.org/10.3390/v16010161
DescriptionFunding: This study was supported by Federal University of ABC (UFABC), São Bernardo do Campo, São Paulo, Brazil and by Wellcome Trust ISSF 204821/Z/16/Z to Michael Nevels (Universityof St Andrews, UK).
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