SARS-CoV-2 ORF8 as a modulator of cytokine induction: evidence and search for molecular mechanisms

Marília Inês Móvio, Giovana Carneiro, Isabella das Graças Lopes Martines, Gilmara Barros de Lima, Sergio Daishi Sasaki, Alexandre Hiroaki Kihara, Emma Poole, Michael Martin Nevels, Maria Christina Carlan de Silva*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)
6 Downloads (Pure)


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.
Original languageEnglish
Article number161
Number of pages15
Issue number1
Publication statusPublished - 22 Jan 2024


  • SARS-CoV-2
  • COVID-19
  • ORF8
  • Cytokine storm


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