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Related Experiment Video

Updated: Jul 18, 2025

Using Reverse Genetics to Manipulate the NSs Gene of the Rift Valley Fever Virus MP-12 Strain to Improve Vaccine Safety and Efficacy
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SARS-CoV-2 ORF8 accessory protein is a virulence factor.

M Bello-Perez1, J Hurtado-Tamayo1, A Z Mykytyn2

  • 1Department of Molecular and Cell Biology, National Center for Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid , Madrid, Spain.

Mbio
|August 25, 2023
PubMed
Summary

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF8 protein contributes to COVID-19 virulence by promoting inflammation and activating macrophages. Targeting ORF8 may offer new therapeutic strategies for COVID-19.

Keywords:
SARS-CoV-2accessory proteinscoronavirusviral pathogenesisvirulence

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Area of Science:

  • Virology
  • Immunology
  • Pathogenesis

Background:

  • The role of SARS-CoV-2 ORF8 in COVID-19 pathogenesis remains unclear.
  • Natural SARS-CoV-2 isolates with ORF8 deletions are linked to milder disease, suggesting ORF8 contributes to virulence.

Purpose of the Study:

  • To investigate the role of SARS-CoV-2 ORF8 in inflammation and macrophage activation.
  • To determine if ORF8 is a potential therapeutic target for COVID-19.

Main Methods:

  • Utilized K18-hACE2 transgenic mice model.
  • Employed organoid-derived human airway cell cultures.

Main Results:

  • Demonstrated ORF8 protein involvement in promoting inflammation.
  • Showed ORF8 activates macrophages in experimental systems.

Conclusions:

  • SARS-CoV-2 ORF8 plays a significant role in COVID-19 pathogenesis through inflammation and macrophage activation.
  • ORF8 protein is identified as a potential therapeutic target for COVID-19 treatment.