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Updated: Aug 30, 2025

Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
Published on: December 23, 2020
SARS-CoV-2 ORF8 is a viral cytokine regulating immune responses
Masako Kohyama1,2, Tatsuya Suzuki3,4, Wataru Nakai1,2
1Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan.
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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