Enterovirus D68 vRNA induces type III IFN production via MDA5

Autor: Chi-Chong Chio, Hio-Wai Chan, Shih-Hsiang Chen, Hsing-I Huang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Virus Research, Vol 339, Iss , Pp 199284- (2024)
Druh dokumentu: article
ISSN: 1872-7492
DOI: 10.1016/j.virusres.2023.199284
Popis: 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.
Databáze: Directory of Open Access Journals