SARS-CoV-2 ORF8 as a Modulator of Cytokine Induction: Evidence and Search for Molecular Mechanisms

被引:3
|
作者
Movio, Marilia Ines [1 ]
de Almeida, Giovana Waner Carneiro [2 ]
Martines, Isabella das Gracas Lopes [2 ]
Barros de Lima, Gilmara [2 ]
Sasaki, Sergio Daishi [2 ]
Kihara, Alexandre Hiroaki [1 ]
Poole, Emma [3 ]
Nevels, Michael [4 ]
da Silva, Maria Cristina Carlan [2 ]
机构
[1] Univ Fed ABC UFABC, Lab Neurogenet, BR-09606070 Sao Bernardo Do Campo, SP, Brazil
[2] Univ Fed ABC UFABC, Ctr Ciencias Nat & Humanas CCNH, BR-09606070 Sao Bernardo Do Campo, SP, Brazil
[3] Univ Cambridge, Dept Pathol, Div Virol, Addenbrookes Hosp, Level 5,Hills Rd, Cambridge CB2 0QQ, England
[4] Univ St Andrews, Sch Biol, St Andrews KY16 9ST, Scotland
来源
VIRUSES-BASEL | 2024年 / 16卷 / 01期
基金
英国惠康基金; 巴西圣保罗研究基金会;
关键词
SARS-CoV-2; COVID-19; ORF8; cytokine storm; TOLL-LIKE RECEPTOR-3; CORONAVIRUS; RESPONSES; COVID-19; INTERFERON; SEVERITY; OUTCOMES; ADULTS; STORM; SARS;
D O I
10.3390/v16010161
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页数:15
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