P-2186. Effects of Knockdown of DDX58 Gene on EV-A71 Replication and Regulation of the RIG-I Receptor Pathway

TL;DR

This study shows that reducing DDX58 limits EV-A71 virus replication and alters immune responses in cells.

Contribution

The novel finding is that DDX58 has a bidirectional regulatory role in the RIG-I pathway during EV-A71 infection.

Findings

Knockdown of DDX58 significantly reduced EV-A71 replication in RD cells.

DDX58 knockdown upregulated antiviral molecules like IRF3, IRF7, and CXCL-10 early post-infection.

DDX58 shows a complex regulatory effect on the RIG-I pathway during EV-A71 infection.

Abstract

This study aimed to investigate the impact of DDX58 knockdown on EV-A71 replication and the activation of the RIG-I-like signaling pathway, and to analyze its role in antiviral immune responses.

DDX58 knockdown was achieved using siRNA transfection in RD cells, followed by infection with EV-A71. mRNA and protein levels of EV-A71, DDX58, and key downstream molecules in the RIG-I pathway were analyzed by qRT-PCR and Western blotting. The concentrations of interferons (IFNα, IFNβ) and CXCL-10 were determined by ELISA.

Knockdown of DDX58 significantly inhibited EV-A71 replication, as evidenced by a reduction in both EV-A71 mRNA and VP1 protein levels. Additionally, the expression of key antiviral signaling molecules, including IRF3, IRF7, and CXCL-10, was upregulated at 24 hours post-infection, but decreased at 36 hours. Notably, the concentrations of IFNα and IFNβ were elevated at 24 hours but showed a decline at later time points.

DDX58 plays a critical role in modulating EV-A71 replication and immune responses, with a complex bidirectional regulatory effect on the RIG-I pathway. These findings suggest that DDX58 could be a potential therapeutic target for regulating antiviral immune responses in EV-A71 infection.

All Authors: No reported disclosures