Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3
Middle East respiratory syndrome coronavirus (MERS-CoV) infection has claimed hundreds of lives and has become a global threat since its emergence in Saudi Arabia in 2012. The ability of MERS-CoV to evade the host innate antiviral response may contribute to its severe pathogenesis. Many MERS-CoV-enc...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2016-01-01
|
| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1038/emi.2016.33 |
| _version_ | 1797679098346078208 |
|---|---|
| author | Pak-Yin Lui Lok-Yin Roy Wong Cheuk-Lai Fung Kam-Leung Siu Man-Lung Yeung Kit-San Yuen Chi-Ping Chan Patrick Chiu-Yat Woo Kwok-Yung Yuen Dong-Yan Jin |
| author_facet | Pak-Yin Lui Lok-Yin Roy Wong Cheuk-Lai Fung Kam-Leung Siu Man-Lung Yeung Kit-San Yuen Chi-Ping Chan Patrick Chiu-Yat Woo Kwok-Yung Yuen Dong-Yan Jin |
| author_sort | Pak-Yin Lui |
| collection | DOAJ |
| description | Middle East respiratory syndrome coronavirus (MERS-CoV) infection has claimed hundreds of lives and has become a global threat since its emergence in Saudi Arabia in 2012. The ability of MERS-CoV to evade the host innate antiviral response may contribute to its severe pathogenesis. Many MERS-CoV-encoded proteins were identified to have interferon (IFN)-antagonizing properties, which correlates well with the reduced IFN levels observed in infected patients and ex vivo models. In this study, we fully characterized the IFN-antagonizing property of the MERS-CoV M protein. Expression of MERS-CoV M protein suppressed type I IFN expression in response to Sendai virus infection or poly(I:C) induction. This suppressive effect was found to be specific for the activation of IFN regulatory factor 3 (IRF3) but not nuclear factor-κB. MERS-CoV M protein interacted with TRAF3 and disrupted TRAF3–TBK1 association leading to reduced IRF3 activation. M proteins from MERS-CoV and SARS-CoV have three highly similar conserved N-terminal transmembrane domains and a C-terminal region. Using chimeric and truncation mutants, the N-terminal transmembrane domains of the MERS-CoV M protein were found to be sufficient for its inhibitory effect on IFN expression, whereas the C-terminal domain was unable to induce this suppression. Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response.Emerging Microbes and Infections (2016) 5, e39; doi:10.1038/emi.2016.33; published online 20 April 2016 |
| first_indexed | 2024-03-11T23:09:30Z |
| format | Article |
| id | doaj.art-7aae242fd8744cf59fbd691cc90fbce9 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-03-11T23:09:30Z |
| publishDate | 2016-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-7aae242fd8744cf59fbd691cc90fbce92023-09-21T12:27:55ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512016-01-01511910.1038/emi.2016.33Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3Pak-Yin Lui0Lok-Yin Roy Wong1Cheuk-Lai Fung2Kam-Leung Siu3Man-Lung Yeung4Kit-San Yuen5Chi-Ping Chan6Patrick Chiu-Yat Woo7Kwok-Yung Yuen8Dong-Yan Jin9School of Biomedical Sciences, The University of Hong Kong, Pokfulam Hong Kong, ChinaSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam Hong Kong, ChinaSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam Hong Kong, ChinaSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam Hong Kong, ChinaDepartment of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong, ChinaSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam Hong Kong, ChinaSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam Hong Kong, ChinaDepartment of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong, ChinaSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam Hong Kong, ChinaMiddle East respiratory syndrome coronavirus (MERS-CoV) infection has claimed hundreds of lives and has become a global threat since its emergence in Saudi Arabia in 2012. The ability of MERS-CoV to evade the host innate antiviral response may contribute to its severe pathogenesis. Many MERS-CoV-encoded proteins were identified to have interferon (IFN)-antagonizing properties, which correlates well with the reduced IFN levels observed in infected patients and ex vivo models. In this study, we fully characterized the IFN-antagonizing property of the MERS-CoV M protein. Expression of MERS-CoV M protein suppressed type I IFN expression in response to Sendai virus infection or poly(I:C) induction. This suppressive effect was found to be specific for the activation of IFN regulatory factor 3 (IRF3) but not nuclear factor-κB. MERS-CoV M protein interacted with TRAF3 and disrupted TRAF3–TBK1 association leading to reduced IRF3 activation. M proteins from MERS-CoV and SARS-CoV have three highly similar conserved N-terminal transmembrane domains and a C-terminal region. Using chimeric and truncation mutants, the N-terminal transmembrane domains of the MERS-CoV M protein were found to be sufficient for its inhibitory effect on IFN expression, whereas the C-terminal domain was unable to induce this suppression. Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response.Emerging Microbes and Infections (2016) 5, e39; doi:10.1038/emi.2016.33; published online 20 April 2016https://www.tandfonline.com/doi/10.1038/emi.2016.33innate antiviral responseIRF3 activationMERS coronavirusRIG-I-like receptorstype I interferons |
| spellingShingle | Pak-Yin Lui Lok-Yin Roy Wong Cheuk-Lai Fung Kam-Leung Siu Man-Lung Yeung Kit-San Yuen Chi-Ping Chan Patrick Chiu-Yat Woo Kwok-Yung Yuen Dong-Yan Jin Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 Emerging Microbes and Infections innate antiviral response IRF3 activation MERS coronavirus RIG-I-like receptors type I interferons |
| title | Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 |
| title_full | Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 |
| title_fullStr | Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 |
| title_full_unstemmed | Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 |
| title_short | Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 |
| title_sort | middle east respiratory syndrome coronavirus m protein suppresses type i interferon expression through the inhibition of tbk1 dependent phosphorylation of irf3 |
| topic | innate antiviral response IRF3 activation MERS coronavirus RIG-I-like receptors type I interferons |
| url | https://www.tandfonline.com/doi/10.1038/emi.2016.33 |
| work_keys_str_mv | AT pakyinlui middleeastrespiratorysyndromecoronavirusmproteinsuppressestypeiinterferonexpressionthroughtheinhibitionoftbk1dependentphosphorylationofirf3 AT lokyinroywong middleeastrespiratorysyndromecoronavirusmproteinsuppressestypeiinterferonexpressionthroughtheinhibitionoftbk1dependentphosphorylationofirf3 AT cheuklaifung middleeastrespiratorysyndromecoronavirusmproteinsuppressestypeiinterferonexpressionthroughtheinhibitionoftbk1dependentphosphorylationofirf3 AT kamleungsiu middleeastrespiratorysyndromecoronavirusmproteinsuppressestypeiinterferonexpressionthroughtheinhibitionoftbk1dependentphosphorylationofirf3 AT manlungyeung middleeastrespiratorysyndromecoronavirusmproteinsuppressestypeiinterferonexpressionthroughtheinhibitionoftbk1dependentphosphorylationofirf3 AT kitsanyuen middleeastrespiratorysyndromecoronavirusmproteinsuppressestypeiinterferonexpressionthroughtheinhibitionoftbk1dependentphosphorylationofirf3 AT chipingchan middleeastrespiratorysyndromecoronavirusmproteinsuppressestypeiinterferonexpressionthroughtheinhibitionoftbk1dependentphosphorylationofirf3 AT patrickchiuyatwoo middleeastrespiratorysyndromecoronavirusmproteinsuppressestypeiinterferonexpressionthroughtheinhibitionoftbk1dependentphosphorylationofirf3 AT kwokyungyuen middleeastrespiratorysyndromecoronavirusmproteinsuppressestypeiinterferonexpressionthroughtheinhibitionoftbk1dependentphosphorylationofirf3 AT dongyanjin middleeastrespiratorysyndromecoronavirusmproteinsuppressestypeiinterferonexpressionthroughtheinhibitionoftbk1dependentphosphorylationofirf3 |