Esterase D enhances type I interferon signal transduction to suppress foot-and-mouth disease virus replication.

Abstract

The enzymatic activities of esterase D (ESD) are involved in many human diseases. However, no antiviral property of ESD has been described to date. Foot-and-mouth disease virus (FMDV) is the etiological agent of foot-and-mouth disease. In this study, we showed that FMDV infection triggered ESD expression. Overexpression of ESD significantly suppressed FMDV replication and knockdown of ESD expression enhanced virus replication, showing an essential antiviral role of ESD. Furthermore, we found that Sendai-virus-induced interferon (IFN) signaling was enhanced by upregulation of ESD, and ESD promoted activation of the IFN-β promoter simulated by IFN regulatory factor (IRF)3 or its upstream molecules (retinoic acid-inducible gene-I, melanoma differentiation-associated protein 5, virus-induced signaling adaptor and TANK binding kinase 1). Detailed analysis revealed that ESD protein enhanced IRF3 phosphorylation during FMDV infection. Overexpression of ESD also promoted the expression of various antiviral interferon-stimulated genes (ISGs) and knockdown of ESD impaired the expression of these antiviral genes during FMDV infection. Our findings demonstrate a new mechanism evolved by ESD to enhance type I IFN signal transduction and suppress viral replication during FMDV infection.

• Authors: Weiwei Li, Zixiang Zhu, Weijun Cao, Fan Yang, Xiangle Zhang, Dan Li, Keshan Zhang, Pengfei Li, Ruoqing Mao, Xiangtao Liu, Haixue Zheng
• Journal: Molecular immunology (Mol Immunol) Vol. 75 Pg. 112-21 (07 2016) ISSN: 1872-9142 [Electronic] England
• PMID: 27267271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Interferon Type I
• Thiolester Hydrolases
• s-formylglutathione hydrolase

Topics

• Animals
• Blotting, Western
• Foot-and-Mouth Disease (immunology)
• Foot-and-Mouth Disease Virus (immunology)
• Gene Knockdown Techniques
• HEK293 Cells
• Humans
• Interferon Type I (immunology, metabolism)
• Real-Time Polymerase Chain Reaction
• Signal Transduction (immunology)
• Swine
• Thiolester Hydrolases (immunology, metabolism)
• Virus Replication (physiology)