Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8

Wu X, Xia T, Shin WJ, Yu KM, Jung W, Herrmann A, Foo SS, Chen W, Zhang P, Lee JS, Poo H, Comhair SAA, Jehi L, Choi YK, Enßer A, Jung JU (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Mbio American Society for Microbiology: mBio / American Society for Microbiology

Book Volume: 13

Journal Issue: 2

DOI: 10.1128/mbio.00402-22

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers cytokine-mediated inflammation, leading to a myriad of clinical presentations in COVID-19. The SARS-CoV-2 open reading frame 8 (ORF8) is a secreted and rapidly evolving glycoprotein. Patients infected with SARS-CoV-2 variants with ORF8 deleted are associated with mild disease outcomes, but the molecular mechanism behind this is unknown. Here, we report that SARS-CoV-2 ORF8 is a viral cytokine that is similar to but distinct from interleukin 17A (IL-17A) as it induces stronger and broader human IL-17 receptor (hIL-17R) signaling than IL-17A. ORF8 primarily targeted blood monocytes and induced the heterodimerization of hIL-17RA and hIL- 17RC, triggering a robust inflammatory response. Transcriptome analysis revealed that besides its activation of the hIL-17R pathway, ORF8 upregulated gene expression for fibrosis signaling and coagulation dysregulation. A naturally occurring ORF8 L84S variant that was highly associated with mild COVID-19 showed reduced hIL- 17RA binding and attenuated inflammatory responses. This study reveals how SARSCoV- 2 ORF8 by a viral mimicry of the IL-17 cytokine contributes to COVID-19 severe inflammation.

Authors with CRIS profile

Alexandra Herrmann Institute of Clinical and Molecular Virology Armin Enßer Medizinische Fakultät

Involved external institutions

Cleveland Clinic US United States (USA) (US) Institute for Basic Science KR Korea, Republic of (KR) Chungnam National University (CNU) KR Korea, Republic of (KR) Korea Research Institute of Bioscience and Biotechnology(KRIBB) KR Korea, Republic of (KR)

How to cite

APA:

Wu, X., Xia, T., Shin, W.-J., Yu, K.-M., Jung, W., Herrmann, A.,... Jung, J.U. (2022). Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8. Mbio, 13(2). https://doi.org/10.1128/mbio.00402-22

MLA:

Wu, Xin, et al. "Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8." Mbio 13.2 (2022).

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