Increased Pathogenicity and Virulence of Middle East Respiratory Syndrome Coronavirus Clade B In Vitro and In Vivo
Copyright © 2020 American Society for Microbiology..
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory disease in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. We isolated the clade B MERS-CoV ChinaGD01 strain from a patient infected during the South Korean MERS outbreak in 2015 and compared the phylogenetics and pathogenicity of MERS-CoV EMC/2012 (clade A) and ChinaGD01 (clade B) in vitro and in vivo Genome alignment analysis showed that most clade-specific mutations occurred in the orf1ab gene, including mutations that were predicted to be potential glycosylation sites. Minor differences in viral growth but no significant differences in plaque size or sensitivity to beta interferon (IFN-β) were detected between these two viruses in vitro ChinaGD01 virus infection induced more weight loss and inflammatory cytokine production in human DPP4-transduced mice. Viral titers were higher in the lungs of ChinaGD01-infected mice than with EMC/2012 infection. Decreased virus-specific CD4+ and CD8+ T cell numbers were detected in the lungs of ChinaGD01-infected mice. In conclusion, MERS-CoV evolution induced changes to reshape its pathogenicity and virulence in vitro and in vivo and to evade adaptive immune response to hinder viral clearance.IMPORTANCE MERS-CoV is an important emerging pathogen and causes severe respiratory infection in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. In this study, we showed that a clade B virus ChinaGD01 strain caused more severe disease in mice, with delayed viral clearance, increased inflammatory cytokines, and decreased antiviral T cell responses, than the early clade A virus EMC/2012. Given the differences in pathogenicity of different clades of MERS-CoV, periodic assessment of currently circulating MERS-CoV is needed to monitor potential severity of zoonotic disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:94 |
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| Enthalten in: |
Journal of virology - 94(2020), 15 vom: 16. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Yanqun [VerfasserIn] |
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| Links: |
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| Themen: |
Interferon Type I |
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| Anmerkungen: |
Date Completed 11.09.2020 Date Revised 16.01.2021 published: Electronic-Print Citation Status MEDLINE |
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| doi: |
10.1128/JVI.00861-20 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310172144 |
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| 100 | 1 | |a Wang, Yanqun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Increased Pathogenicity and Virulence of Middle East Respiratory Syndrome Coronavirus Clade B In Vitro and In Vivo |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 11.09.2020 | ||
| 500 | |a Date Revised 16.01.2021 | ||
| 500 | |a published: Electronic-Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 American Society for Microbiology. | ||
| 520 | |a Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory disease in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. We isolated the clade B MERS-CoV ChinaGD01 strain from a patient infected during the South Korean MERS outbreak in 2015 and compared the phylogenetics and pathogenicity of MERS-CoV EMC/2012 (clade A) and ChinaGD01 (clade B) in vitro and in vivo Genome alignment analysis showed that most clade-specific mutations occurred in the orf1ab gene, including mutations that were predicted to be potential glycosylation sites. Minor differences in viral growth but no significant differences in plaque size or sensitivity to beta interferon (IFN-β) were detected between these two viruses in vitro ChinaGD01 virus infection induced more weight loss and inflammatory cytokine production in human DPP4-transduced mice. Viral titers were higher in the lungs of ChinaGD01-infected mice than with EMC/2012 infection. Decreased virus-specific CD4+ and CD8+ T cell numbers were detected in the lungs of ChinaGD01-infected mice. In conclusion, MERS-CoV evolution induced changes to reshape its pathogenicity and virulence in vitro and in vivo and to evade adaptive immune response to hinder viral clearance.IMPORTANCE MERS-CoV is an important emerging pathogen and causes severe respiratory infection in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. In this study, we showed that a clade B virus ChinaGD01 strain caused more severe disease in mice, with delayed viral clearance, increased inflammatory cytokines, and decreased antiviral T cell responses, than the early clade A virus EMC/2012. Given the differences in pathogenicity of different clades of MERS-CoV, periodic assessment of currently circulating MERS-CoV is needed to monitor potential severity of zoonotic disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a MERS-CoV | |
| 650 | 4 | |a T cell response | |
| 650 | 4 | |a pathogenicity | |
| 650 | 4 | |a phylogenetics | |
| 650 | 4 | |a virulence | |
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| 650 | 7 | |a RNA, Viral |2 NLM | |
| 700 | 1 | |a Sun, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiaobo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Airu |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Wenda |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, De-Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Gan, Mian |e verfasserin |4 aut | |
| 700 | 1 | |a Niu, Xuefeng |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhaoyong |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Yongxia |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Shuxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Mok, Chris Ka Pun |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Zifeng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhongfang |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Wenjie |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yimin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Rongchang |e verfasserin |4 aut | |
| 700 | 1 | |a Peiris, Malik |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Nanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jingxian |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jicheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jincun |e verfasserin |4 aut | |
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