Identification and characterization of GLDC as host susceptibility gene to severe influenza
Abstract Glycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibilit...
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| Format: | Article |
| Language: | English |
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Springer Nature
2018-11-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201809528 |
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| author | Jie Zhou Dong Wang Bosco Ho‐Yin Wong Cun Li Vincent Kwok‐Man Poon Lei Wen Xiaoyu Zhao Man Chun Chiu Xiaojuan Liu Ziwei Ye Shuofeng Yuan Kong‐Hung Sze Jasper Fuk‐Woo Chan Hin Chu Kelvin Kai‐Wang To Kwok Yung Yuen |
| author_facet | Jie Zhou Dong Wang Bosco Ho‐Yin Wong Cun Li Vincent Kwok‐Man Poon Lei Wen Xiaoyu Zhao Man Chun Chiu Xiaojuan Liu Ziwei Ye Shuofeng Yuan Kong‐Hung Sze Jasper Fuk‐Woo Chan Hin Chu Kelvin Kai‐Wang To Kwok Yung Yuen |
| author_sort | Jie Zhou |
| collection | DOAJ |
| description | Abstract Glycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFNβ‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significantly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans. |
| format | Article |
| id | doaj-art-665342808ef74e9fb985c5b8bd62c4b1 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2018-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-665342808ef74e9fb985c5b8bd62c4b12025-08-20T04:02:56ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-11-0111111410.15252/emmm.201809528Identification and characterization of GLDC as host susceptibility gene to severe influenzaJie Zhou0Dong Wang1Bosco Ho‐Yin Wong2Cun Li3Vincent Kwok‐Man Poon4Lei Wen5Xiaoyu Zhao6Man Chun Chiu7Xiaojuan Liu8Ziwei Ye9Shuofeng Yuan10Kong‐Hung Sze11Jasper Fuk‐Woo Chan12Hin Chu13Kelvin Kai‐Wang To14Kwok Yung Yuen15State Key Laboratory of Emerging Infectious Diseases, The University of Hong KongDepartment of Microbiology, The University of Hong KongDepartment of Microbiology, The University of Hong KongDepartment of Microbiology, The University of Hong KongDepartment of Microbiology, The University of Hong KongDepartment of Microbiology, The University of Hong KongDepartment of Microbiology, The University of Hong KongDepartment of Microbiology, The University of Hong KongDepartment of Microbiology, The University of Hong KongDepartment of Microbiology, The University of Hong KongDepartment of Microbiology, The University of Hong KongDepartment of Microbiology, The University of Hong KongState Key Laboratory of Emerging Infectious Diseases, The University of Hong KongState Key Laboratory of Emerging Infectious Diseases, The University of Hong KongState Key Laboratory of Emerging Infectious Diseases, The University of Hong KongState Key Laboratory of Emerging Infectious Diseases, The University of Hong KongAbstract Glycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFNβ‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significantly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans.https://doi.org/10.15252/emmm.201809528antiviral responsegenetic susceptibilityGLDCsevere influenzaviral replication |
| spellingShingle | Jie Zhou Dong Wang Bosco Ho‐Yin Wong Cun Li Vincent Kwok‐Man Poon Lei Wen Xiaoyu Zhao Man Chun Chiu Xiaojuan Liu Ziwei Ye Shuofeng Yuan Kong‐Hung Sze Jasper Fuk‐Woo Chan Hin Chu Kelvin Kai‐Wang To Kwok Yung Yuen Identification and characterization of GLDC as host susceptibility gene to severe influenza EMBO Molecular Medicine antiviral response genetic susceptibility GLDC severe influenza viral replication |
| title | Identification and characterization of GLDC as host susceptibility gene to severe influenza |
| title_full | Identification and characterization of GLDC as host susceptibility gene to severe influenza |
| title_fullStr | Identification and characterization of GLDC as host susceptibility gene to severe influenza |
| title_full_unstemmed | Identification and characterization of GLDC as host susceptibility gene to severe influenza |
| title_short | Identification and characterization of GLDC as host susceptibility gene to severe influenza |
| title_sort | identification and characterization of gldc as host susceptibility gene to severe influenza |
| topic | antiviral response genetic susceptibility GLDC severe influenza viral replication |
| url | https://doi.org/10.15252/emmm.201809528 |
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