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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...

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Autores principales: 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.
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
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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.
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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
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