Severe pneumonia and pathogenic damage in human airway epithelium caused by Coxsackievirus B4
Coxsackievirus B4 (CVB4) has one of the highest proportions of fatal outcomes of other enterovirus serotypes. However, the pathogenesis of severe respiratory disease caused by CVB4 infection remains unclear. In this study, 3 of 42 (7.2%, GZ-R6, GZ-R7 and GZ-R8) patients with severe pneumonia tested...
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Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2261560 |
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| author | Jing Dai Duo Xu Chao Yang Huan Wang Dehui Chen Zhengshi Lin Shuyan Qiu Li Zhang Xiao Li Xingui Tian Qian Liu Yujun Cui Rong Zhou Wenkuan Liu |
| author_facet | Jing Dai Duo Xu Chao Yang Huan Wang Dehui Chen Zhengshi Lin Shuyan Qiu Li Zhang Xiao Li Xingui Tian Qian Liu Yujun Cui Rong Zhou Wenkuan Liu |
| author_sort | Jing Dai |
| collection | DOAJ |
| description | Coxsackievirus B4 (CVB4) has one of the highest proportions of fatal outcomes of other enterovirus serotypes. However, the pathogenesis of severe respiratory disease caused by CVB4 infection remains unclear. In this study, 3 of 42 (7.2%, GZ-R6, GZ-R7 and GZ-R8) patients with severe pneumonia tested positive for CVB4 infection in southern China. Three full-length genomes of pneumonia-derived CVB4 were sequenced and annotated for the first time, showing their high nucleotide similarity and clustering within genotype V. To analyze the pathogenic damage caused by CVB4 in the lungs, a well-differentiated human airway epithelium (HAE) was established and infected with the pneumonia-derived CVB4 isolate GZ-R6. The outcome was compared with that of a severe hand-foot-mouth disease (HFMD)-derived CVB4 strain GZ-HFM01. Compared with HFMD-derived CVB4, pneumonia-derived CVB4 caused more intense and rapid disruption of HAE polarity, leading to tight-junction barrier disruption, loss of cilia, and airway epithelial cell hypertrophy. More pneumonia-derived CVB4 were released from the basolateral side of the HAE than HFMD-derived CVB4. Of the 18 cytokines tested, only IL-6 and IL-1b secretion significantly increased on bilateral sides of HAE during the early stage of pneumonia-derived CVB4 infection, while multiple cytokine secretions significantly increased in HFMD-derived CVB4-infected HAE. HFMD-derived CVB4 exhibited stronger neurovirulence in the human neuroblastoma cells SH-SY5Y than pneumonia-derived CVB4, which is consistent with the clinical manifestations of patients infected with these two viruses. This study has increased the depth of our knowledge of severe pneumonia infection caused by CVB4 and will benefit its prevention and treatment. |
| format | Article |
| id | doaj-art-d50b86ac1a6d4d34b7bac8b2c8f1b642 |
| institution | Kabale University |
| issn | 2222-1751 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-d50b86ac1a6d4d34b7bac8b2c8f1b6422025-08-20T03:29:13ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2261560Severe pneumonia and pathogenic damage in human airway epithelium caused by Coxsackievirus B4Jing Dai0Duo Xu1Chao Yang2Huan Wang3Dehui Chen4Zhengshi Lin5Shuyan Qiu6Li Zhang7Xiao Li8Xingui Tian9Qian Liu10Yujun Cui11Rong Zhou12Wenkuan Liu13State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaThe Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, People’s Republic of ChinaScientific Research Center, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaScientific Research Center, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People’s Republic of ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCoxsackievirus B4 (CVB4) has one of the highest proportions of fatal outcomes of other enterovirus serotypes. However, the pathogenesis of severe respiratory disease caused by CVB4 infection remains unclear. In this study, 3 of 42 (7.2%, GZ-R6, GZ-R7 and GZ-R8) patients with severe pneumonia tested positive for CVB4 infection in southern China. Three full-length genomes of pneumonia-derived CVB4 were sequenced and annotated for the first time, showing their high nucleotide similarity and clustering within genotype V. To analyze the pathogenic damage caused by CVB4 in the lungs, a well-differentiated human airway epithelium (HAE) was established and infected with the pneumonia-derived CVB4 isolate GZ-R6. The outcome was compared with that of a severe hand-foot-mouth disease (HFMD)-derived CVB4 strain GZ-HFM01. Compared with HFMD-derived CVB4, pneumonia-derived CVB4 caused more intense and rapid disruption of HAE polarity, leading to tight-junction barrier disruption, loss of cilia, and airway epithelial cell hypertrophy. More pneumonia-derived CVB4 were released from the basolateral side of the HAE than HFMD-derived CVB4. Of the 18 cytokines tested, only IL-6 and IL-1b secretion significantly increased on bilateral sides of HAE during the early stage of pneumonia-derived CVB4 infection, while multiple cytokine secretions significantly increased in HFMD-derived CVB4-infected HAE. HFMD-derived CVB4 exhibited stronger neurovirulence in the human neuroblastoma cells SH-SY5Y than pneumonia-derived CVB4, which is consistent with the clinical manifestations of patients infected with these two viruses. This study has increased the depth of our knowledge of severe pneumonia infection caused by CVB4 and will benefit its prevention and treatment.https://www.tandfonline.com/doi/10.1080/22221751.2023.2261560Coxsackievirus B4severe pneumoniahand-foot-mouth disease (HFMD)pathogenic damagehuman airway epitheliumfull-length genome |
| spellingShingle | Jing Dai Duo Xu Chao Yang Huan Wang Dehui Chen Zhengshi Lin Shuyan Qiu Li Zhang Xiao Li Xingui Tian Qian Liu Yujun Cui Rong Zhou Wenkuan Liu Severe pneumonia and pathogenic damage in human airway epithelium caused by Coxsackievirus B4 Emerging Microbes and Infections Coxsackievirus B4 severe pneumonia hand-foot-mouth disease (HFMD) pathogenic damage human airway epithelium full-length genome |
| title | Severe pneumonia and pathogenic damage in human airway epithelium caused by Coxsackievirus B4 |
| title_full | Severe pneumonia and pathogenic damage in human airway epithelium caused by Coxsackievirus B4 |
| title_fullStr | Severe pneumonia and pathogenic damage in human airway epithelium caused by Coxsackievirus B4 |
| title_full_unstemmed | Severe pneumonia and pathogenic damage in human airway epithelium caused by Coxsackievirus B4 |
| title_short | Severe pneumonia and pathogenic damage in human airway epithelium caused by Coxsackievirus B4 |
| title_sort | severe pneumonia and pathogenic damage in human airway epithelium caused by coxsackievirus b4 |
| topic | Coxsackievirus B4 severe pneumonia hand-foot-mouth disease (HFMD) pathogenic damage human airway epithelium full-length genome |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2261560 |
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