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Reviews of "SARS-CoV-2 ORF8 Modulates Lung Inflammation and Clinical Disease Progression"

Reviewers: Y Tan & K M Lai (National University of Singapore) | 📗📗📗📗◻️ • J Chen (University of Alaska Fairbanks) | 📗📗📗📗◻️• M Bouvier (University of Illinois) | 📗📗📗📗◻️

Published onOct 13, 2023
Reviews of "SARS-CoV-2 ORF8 Modulates Lung Inflammation and Clinical Disease Progression"
key-enterThis Pub is a Review of
SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression
SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression

The virus severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of the current COVID-19 pandemic. It possesses a large 30 kilobase (kb) genome that encodes structural, non-structural, and accessory proteins. Although not necessary to cause disease, these accessory proteins are known to influence viral replication and pathogenesis. Through the synthesis of novel infectious clones of SARS-CoV-2 that lack one or more of the accessory proteins of the virus, we have found that one of these accessory proteins, ORF8, is critical for the modulation of the host inflammatory response. Mice infected with a SARS-CoV-2 virus lacking ORF8 exhibit increased weight loss and exacerbated macrophage infiltration into the lungs. Additionally, infection of mice with recombinant SARS-CoV-2 viruses encoding ORF8 mutations found in variants of concern reveal that naturally occurring mutations in this protein influence disease severity. Our studies with a virus lacking this ORF8 protein and viruses possessing naturally occurring point mutations in this protein demonstrate that this protein impacts pathogenesis.

To read the original manuscript, click the link above.

Summary of Reviews: This preprint investigates the role of SARS-CoV-2 accessory protein ORF8 in modulating host inflammation and disease progression in mice. Reviewers provided thoughtful critiques, highlighting how the ORF8 deletion virus elicited increased lung inflammation and macrophage activation compared to wildtype virus. They offered constructive suggestions like correlating ORF8 mutations with clinical outcomes in humans. While finding the central conclusions valid and technically sound, reviewers noted opportunities to strengthen connections to human disease and provide more detailed critique. The lay summaries focused on the role of ORF8 in modulating pathogenesis. Overall, reviewers rated this preprint as reliable, though further validation and mechanistic dissection of ORF8 would be beneficial. This preprint makes a meaningful contribution to understanding ORF8 immune modulation, though additional work could strengthen the translational relevance.

Reviewer 1 (Yee-Joo T & Kah Man L…) | 📗📗📗📗◻️

Reviewer 2 (Jack C…) | 📗📗📗📗◻️

Reviewer 3 (Marlene B…) | 📗📗📗📗◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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