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SARS-CoV-2 ORF8 is a viral cytokine regulating immune responses. | LitMetric

AI Article Synopsis

  • - The study investigates the ORF8 protein from SARS-CoV-2, identifying its role in causing severe pneumonia and lung inflammation in COVID-19 patients.
  • - Researchers created a version of the virus without ORF8 and found reduced lung inflammation in infected hamsters, suggesting ORF8's involvement in the disease's severity.
  • - Elevated levels of ORF8 protein in serum are linked to inflammation in patients, indicating that targeting ORF8 could provide new treatment options for severe COVID-19 cases.

Article Abstract

Many patients with severe COVID-19 suffer from pneumonia and the elucidation of the mechanisms underlying the development of this severe condition is important. The in vivo function of the ORF8 protein secreted by SARS-CoV-2 is not well understood. Here, we analyzed the function of ORF8 protein by generating ORF8-knockout SARS-CoV-2 and found that the lung inflammation observed in wild-type SARS-CoV-2-infected hamsters was decreased in ORF8-knockout SARS-CoV-2-infected hamsters. Administration of recombinant ORF8 protein to hamsters also induced lymphocyte infiltration into the lungs. Similar pro-inflammatory cytokine production was observed in primary human monocytes treated with recombinant ORF8 protein. Furthermore, we demonstrated that the serum ORF8 protein levels are well-correlated with clinical markers of inflammation. These results demonstrated that the ORF8 protein is a SARS-CoV-2 viral cytokine involved in the immune dysregulation observed in COVID-19 patients, and that the ORF8 protein could be a novel therapeutic target in severe COVID-19 patients.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9494306PMC
http://dx.doi.org/10.1093/intimm/dxac044DOI Listing

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