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Reviews of "The Unique ORF8 Protein From SARS-CoV-2 Binds to Human Dendritic Cells and Induces a Hyper-inflammatory Cytokine Storm"

Reviewers: Y Zhang (Sun Yat-sen University) | 📗📗📗📗◻️ • J Díaz (Universidad Autónoma del Estado de Morelos) | 📗📗📗📗◻️

Published onJul 15, 2022
Reviews of "The Unique ORF8 Protein From SARS-CoV-2 Binds to Human Dendritic Cells and Induces a Hyper-inflammatory Cytokine Storm"
key-enterThis Pub is a Review of
The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm
Description

AbstractThe novel coronavirus pandemic, whose first outbreak was reported in December 2019 in Wuhan, China (COVID-19), is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Tissue damage caused by the virus 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 many viral infections the recruitment of monocytes into the lung and their differentiation to dendritic cells (DCs) are seen as a response to the viral infection. DCs are critical players in the development of the acute lung inflammation that causes ARDS. Here we focus on the interaction of the ORF8 protein, a specific SARS-CoV-2 open reading frame protein, with dendritic cells (DCs). We show that ORF8 binds to dendritic cells, causes a pre-maturation of differentiating DCs, and induces the secretion of multiple pro-inflammatory cytokines by these cells. In addition, we identified dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) as a possible interaction partner of ORF8 on dendritic cells. Blockade of ORF8 signaling leads to reduced production of IL-1β, IL-6, IL-12p70, TNF-α, MCP-1 (CCL2), and IL-10 by dendritic cells. Analysis of patient sera with high anti-ORF8 antibody titers showed that there was nearly no neutralization of the ORF8 protein and its function. Therefore, a neutralizing antibody that has the capacity of blocking the cytokine and chemokine response mediated by ORF8 protein might be an essential and novel additional step in the therapy of severe SARS-CoV-2 cases.

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Summary of Reviews: This study demonstrates that neutralizing ORF8 may be a promising route of reducing immune hyperreactivity as a cause of severe disease. The claims presented in this work are reliable but could be strengthened through further statistical analysis.

Reviewer 1 (Yiwen Z…) | 📗📗📗📗◻️

Reviewer 2 (José D…) | 📗📗📗📗◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

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