Cargando…
Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8
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 var...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040823/ https://www.ncbi.nlm.nih.gov/pubmed/35343786 http://dx.doi.org/10.1128/mbio.00402-22 |
_version_ | 1784694414288879616 |
---|---|
author | Wu, Xin Xia, Tian Shin, Woo-Jin Yu, Kwang-Min Jung, Wooram Herrmann, Alexandra Foo, Suan-Sin Chen, Weiqiang Zhang, Pengfei Lee, Jong-Soo Poo, Haryoung Comhair, Suzy A. A. Jehi, Lara Choi, Young Ki Ensser, Armin Jung, Jae U. |
author_facet | Wu, Xin Xia, Tian Shin, Woo-Jin Yu, Kwang-Min Jung, Wooram Herrmann, Alexandra Foo, Suan-Sin Chen, Weiqiang Zhang, Pengfei Lee, Jong-Soo Poo, Haryoung Comhair, Suzy A. A. Jehi, Lara Choi, Young Ki Ensser, Armin Jung, Jae U. |
author_sort | Wu, Xin |
collection | PubMed |
description | 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 SARS-CoV-2 ORF8 by a viral mimicry of the IL-17 cytokine contributes to COVID-19 severe inflammation. |
format | Online Article Text |
id | pubmed-9040823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-90408232022-04-27 Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8 Wu, Xin Xia, Tian Shin, Woo-Jin Yu, Kwang-Min Jung, Wooram Herrmann, Alexandra Foo, Suan-Sin Chen, Weiqiang Zhang, Pengfei Lee, Jong-Soo Poo, Haryoung Comhair, Suzy A. A. Jehi, Lara Choi, Young Ki Ensser, Armin Jung, Jae U. mBio Research Article 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 SARS-CoV-2 ORF8 by a viral mimicry of the IL-17 cytokine contributes to COVID-19 severe inflammation. American Society for Microbiology 2022-03-28 /pmc/articles/PMC9040823/ /pubmed/35343786 http://dx.doi.org/10.1128/mbio.00402-22 Text en Copyright © 2022 Wu et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Wu, Xin Xia, Tian Shin, Woo-Jin Yu, Kwang-Min Jung, Wooram Herrmann, Alexandra Foo, Suan-Sin Chen, Weiqiang Zhang, Pengfei Lee, Jong-Soo Poo, Haryoung Comhair, Suzy A. A. Jehi, Lara Choi, Young Ki Ensser, Armin Jung, Jae U. Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8 |
title | Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8 |
title_full | Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8 |
title_fullStr | Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8 |
title_full_unstemmed | Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8 |
title_short | Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8 |
title_sort | viral mimicry of interleukin-17a by sars-cov-2 orf8 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040823/ https://www.ncbi.nlm.nih.gov/pubmed/35343786 http://dx.doi.org/10.1128/mbio.00402-22 |
work_keys_str_mv | AT wuxin viralmimicryofinterleukin17abysarscov2orf8 AT xiatian viralmimicryofinterleukin17abysarscov2orf8 AT shinwoojin viralmimicryofinterleukin17abysarscov2orf8 AT yukwangmin viralmimicryofinterleukin17abysarscov2orf8 AT jungwooram viralmimicryofinterleukin17abysarscov2orf8 AT herrmannalexandra viralmimicryofinterleukin17abysarscov2orf8 AT foosuansin viralmimicryofinterleukin17abysarscov2orf8 AT chenweiqiang viralmimicryofinterleukin17abysarscov2orf8 AT zhangpengfei viralmimicryofinterleukin17abysarscov2orf8 AT leejongsoo viralmimicryofinterleukin17abysarscov2orf8 AT pooharyoung viralmimicryofinterleukin17abysarscov2orf8 AT comhairsuzyaa viralmimicryofinterleukin17abysarscov2orf8 AT jehilara viralmimicryofinterleukin17abysarscov2orf8 AT choiyoungki viralmimicryofinterleukin17abysarscov2orf8 AT ensserarmin viralmimicryofinterleukin17abysarscov2orf8 AT jungjaeu viralmimicryofinterleukin17abysarscov2orf8 |