Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Marilia Inês Móvio
,
Giovana Carneiro
,
Isabella Lopes Martines
,
Gilmara Barros de Lima
ORCID logo ,
Sergio Daishi Sasaki
ORCID logo ,
Alexandre Hiroaki KIhara
,
Emma Poole
,
Michael Nevels
ORCID logo ,
Maria Cristina Carlan da Silva
*
Version 1 : Received: 29 November 2023 / Approved: 29 November 2023 / Online: 30 November 2023 (10:29:01 CET)

A peer-reviewed article of this Preprint also exists.

Móvio, M.I.; Almeida, G.W.C.; Martines, I.G.L.; Barros de Lima, G.; Sasaki, S.D.; Kihara, A.H.; Poole, E.; Nevels, M.; Carlan da Silva, M.C. SARS-CoV-2 ORF8 as a Modulator of Cytokine Induction: Evidence and Search for Molecular Mechanisms. Viruses 2024, 16, 161. Móvio, M.I.; Almeida, G.W.C.; Martines, I.G.L.; Barros de Lima, G.; Sasaki, S.D.; Kihara, A.H.; Poole, E.; Nevels, M.; Carlan da Silva, M.C. SARS-CoV-2 ORF8 as a Modulator of Cytokine Induction: Evidence and Search for Molecular Mechanisms. Viruses 2024, 16, 161.

Abstract

Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction of pro-inflammatory cytokines, resulting in damage to the lungs and other organs. This remarkable increase in cytokines and other inflammatory molecules is primary caused by viral proteins, in particular ORF8, a unique accessory protein specific to SARS-CoV-2. In addition to its role in cytokine induction, ORF8 is attributed with various other functions, including its ability to evade type I interferon responses. Despite the evidence, the mechanisms through which ORF8 exerts these functions remains a subject of controversy. In this mini review, we discuss the multifaceted roles of ORF8 as a modulator of cytokine response, focusing on type I interferon and IL-6. We also discuss data from our studies indicating 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).

Keywords

SARS CoV-2; COVID-19; ORF8, cytokine storm

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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