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SARS-CoV-2 ORF8 is a viral cytokine regulating immune responses
Masako Kohyama; Tatsuya Suzuki; Wataru Nakai; Chikako Ono; Sumiko Matsuoka; Koichi Iwatani; Yafei Liu; Yusuke Sakai; Atsushi Nakagawa; Keisuke Tomii; Koichiro Ohmura; Masato Okada; Yoshiharu Matsuura; Shiro Oshima; Yusuke Maeda; Toru Okamoto; Hisashi Arase.
Afiliación
  • Masako Kohyama; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University
  • Tatsuya Suzuki; Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University
  • Wataru Nakai; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka
  • Chikako Ono; Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University
  • Sumiko Matsuoka; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University
  • Koichi Iwatani; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University
  • Yafei Liu; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University
  • Yusuke Sakai; Department of Veterinary Pathology, Yamaguchi University
  • Atsushi Nakagawa; Department of Respiratory Medicine, Kobe City Medical Center General Hospital
  • Keisuke Tomii; Department of Respiratory Medicine, Kobe City Medical Center General Hospital
  • Koichiro Ohmura; Department of Rheumatology, Kobe City Medical Center General Hospital
  • Masato Okada; Department of Oncogene Research, Research Institute for Microbial Diseases
  • Yoshiharu Matsuura; Department of Molecular Virology, Research Institute for Microbial Diseases
  • Shiro Oshima; Department of Clinical Research, Osaka Minami Medical Center, Osaka
  • Yusuke Maeda; Department of Molecular Virology, Research Institute for Microbial Diseases
  • Toru Okamoto; Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases
  • Hisashi Arase; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-502275
ABSTRACT
Many patients with severe COVID-19 suffer from pneumonia, and thus elucidation of the mechanisms underlying the development of such severe pneumonia is important. The ORF8 protein is a secreted protein of SARS-CoV-2, whose in vivo function is not well understood. Here, we analyzed the function of ORF8 protein by generating ORF8-knockout SARS-CoV-2. We 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 demonstrate that the serum ORF8 protein levels are correlated well with clinical markers of inflammation. These results demonstrated that the ORF8 protein is a viral cytokine of SARS-CoV-2 involved in the 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.
Licencia
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2022 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2022 Tipo del documento: Preprint