Enterovirus D68 vRNA induces type III IFN production via MDA5

Chi Chong Chio, Hio Wai Chan, Shih Hsiang Chen, Hsing I. Huang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

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.

Original languageEnglish
Article number199284
Pages (from-to)199284
JournalVirus Research
Volume339
DOIs
StatePublished - 02 01 2024

Bibliographical note

Copyright © 2023. Published by Elsevier B.V.

Keywords

  • Calu-3
  • Ev-D68
  • IFN-λ
  • MDA5
  • vRNA
  • Enterovirus Infections
  • Neuromuscular Diseases
  • Humans
  • Interferon Lambda
  • Respiratory System
  • Child
  • Enterovirus D, Human/genetics

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