Enterovirus D68 vRNA induces type III IFN production via MDA5
Enterovirus D68 (EV-D68) primarily spreads through the respiratory tract and causes respiratory symptoms in children and acute flaccid myelitis (AFM). Type III interferons (IFNs) play a critical role in inhibiting viral growth in respiratory epithelial cells. However, the mechanism by which EV-D68 i...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Virus Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0168170223002460 |
| _version_ | 1797405530505871360 |
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| author | Chi-Chong Chio Hio-Wai Chan Shih-Hsiang Chen Hsing-I Huang |
| author_facet | Chi-Chong Chio Hio-Wai Chan Shih-Hsiang Chen Hsing-I Huang |
| author_sort | Chi-Chong Chio |
| collection | DOAJ |
| description | Enterovirus D68 (EV-D68) primarily spreads through the respiratory tract and causes respiratory symptoms in children and acute flaccid myelitis (AFM). Type III interferons (IFNs) play a critical role in inhibiting viral growth in respiratory epithelial cells. However, the mechanism by which EV-D68 induces type III IFN production is not yet fully understood. In this study, we show that EV-D68 infection stimulates Calu-3 cells to secrete IFN-λ. The transfection of EV-D68 viral RNA (vRNA) stimulated IFN-λ via MDA5. Furthermore, our findings provide evidence that EV-D68 infection also induces MDA5- IRF3/IRF7-mediated IFN-λ. In addition, we discovered that EV-D68 infection downregulated MDA5 expression. Knockdown of MDA5 increased EV-D68 replication in Calu-3 cells. Finally, we demonstrated that the IFN-λ1 and IFN-λ2/3 proteins effectively inhibit EV-D68 infection in respiratory epithelial cells. In summary, our study shows that EV-D68 induces type III IFN production via the activated MDA5-IRF3/IRF7 pathway and that type III IFNs inhibit EV-D68 replication in Calu-3 cells. |
| first_indexed | 2024-03-09T03:11:21Z |
| format | Article |
| id | doaj.art-c9c73f6aef7f45a499788ac15438b7a0 |
| institution | Directory Open Access Journal |
| issn | 1872-7492 |
| language | English |
| last_indexed | 2024-03-09T03:11:21Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Virus Research |
| spelling | doaj.art-c9c73f6aef7f45a499788ac15438b7a02023-12-04T05:21:18ZengElsevierVirus Research1872-74922024-01-01339199284Enterovirus D68 vRNA induces type III IFN production via MDA5Chi-Chong Chio0Hio-Wai Chan1Shih-Hsiang Chen2Hsing-I Huang3Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, TaiwanResearch Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, TaiwanDivision of Pediatric Hematology/Oncology, Linkou Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan; College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, TaiwanResearch Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan; Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan; Corresponding author at: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, TaiwanEnterovirus D68 (EV-D68) primarily spreads through the respiratory tract and causes respiratory symptoms in children and acute flaccid myelitis (AFM). Type III interferons (IFNs) play a critical role in inhibiting viral growth in respiratory epithelial cells. However, the mechanism by which EV-D68 induces type III IFN production is not yet fully understood. In this study, we show that EV-D68 infection stimulates Calu-3 cells to secrete IFN-λ. The transfection of EV-D68 viral RNA (vRNA) stimulated IFN-λ via MDA5. Furthermore, our findings provide evidence that EV-D68 infection also induces MDA5- IRF3/IRF7-mediated IFN-λ. In addition, we discovered that EV-D68 infection downregulated MDA5 expression. Knockdown of MDA5 increased EV-D68 replication in Calu-3 cells. Finally, we demonstrated that the IFN-λ1 and IFN-λ2/3 proteins effectively inhibit EV-D68 infection in respiratory epithelial cells. In summary, our study shows that EV-D68 induces type III IFN production via the activated MDA5-IRF3/IRF7 pathway and that type III IFNs inhibit EV-D68 replication in Calu-3 cells.http://www.sciencedirect.com/science/article/pii/S0168170223002460Ev-D68Calu-3IFN-λvRNAMDA5 |
| spellingShingle | Chi-Chong Chio Hio-Wai Chan Shih-Hsiang Chen Hsing-I Huang Enterovirus D68 vRNA induces type III IFN production via MDA5 Virus Research Ev-D68 Calu-3 IFN-λ vRNA MDA5 |
| title | Enterovirus D68 vRNA induces type III IFN production via MDA5 |
| title_full | Enterovirus D68 vRNA induces type III IFN production via MDA5 |
| title_fullStr | Enterovirus D68 vRNA induces type III IFN production via MDA5 |
| title_full_unstemmed | Enterovirus D68 vRNA induces type III IFN production via MDA5 |
| title_short | Enterovirus D68 vRNA induces type III IFN production via MDA5 |
| title_sort | enterovirus d68 vrna induces type iii ifn production via mda5 |
| topic | Ev-D68 Calu-3 IFN-λ vRNA MDA5 |
| url | http://www.sciencedirect.com/science/article/pii/S0168170223002460 |
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