Multiple Porcine Innate Immune Signaling Pathways Are Involved in the Anti-PEDV Response

Youwen Zhang; Yulin Xu; Sen Jiang; Shaohua Sun; Jiajia Zhang; Jia Luo; Qi Cao; Wanglong Zheng; François Meurens; Nanhua Chen; Jianzhong Zhu

doi:10.3390/v15081629

Multiple Porcine Innate Immune Signaling Pathways Are Involved in the Anti-PEDV Response

Viruses. 2023 Jul 26;15(8):1629. doi: 10.3390/v15081629.

Authors

Youwen Zhang^{1

2

3

4}, Yulin Xu^{1

2

3

4}, Sen Jiang^{1

2

3

4}, Shaohua Sun^{1

2

3

4}, Jiajia Zhang^{1

2

3

4}, Jia Luo^{1

2

3

4}, Qi Cao^{1

2

3

4}, Wanglong Zheng^{1

2

3

4}, François Meurens^{5

6}, Nanhua Chen^{1

2

3

4}, Jianzhong Zhu^{1

2

3

4}

Affiliations

¹ College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
² Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou 225009, China.
³ Comparative Medicine Research Institute, Yangzhou University, Yangzhou 225009, China.
⁴ Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
⁵ Swine and Poultry Infectious Diseases Research Center, Faculty of Veterinary Medicine, University of Montreal, St. Hyacinthe, QC J2S 2M2, Canada.
⁶ Department of Veterinary Microbiology and Immunology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E2, Canada.

Abstract

Porcine epidemic diarrhea virus (PEDV) has caused great damage to the global pig industry. Innate immunity plays a significant role in resisting viral infection; however, the exact role of innate immunity in the anti-PEDV response has not been fully elucidated. In this study, we observed that various porcine innate immune signaling adaptors are involved in anti-PEDV (AJ1102-like strain) activity in transfected Vero cells. Among these, TRIF and MAVS showed the strongest anti-PEDV activity. The endogenous TRIF, MAVS, and STING were selected for further examination of anti-PEDV activity. Agonist stimulation experiments showed that TRIF, MAVS, and STING signaling all have obvious anti-PEDV activity. The siRNA knockdown assay showed that TRIF, MAVS, and STING are also all involved in anti-PEDV response, and their remarkable effects on PEDV replication were confirmed in TRIF^-/-, MAVS^-/- and STING^-/- Vero cells via the CRISPR approach. For further verification, the anti-PEDV activity of TRIF, MAVS, and STING could be reproduced in porcine IPEC-DQ cells treated with siRNAs. In summary, this study reveals that multiple pattern-recognition receptor (PRR) signaling pathways of porcine innate immunity play an important role in the anti-PEDV infection, providing new and useful antiviral knowledge for prevention and control of PEDV spreading.

Keywords: PEDV; knockout; pattern recognition receptor (PRR); porcine innate immunity; siRNA; signaling adaptors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Vesicular Transport
Animals
Chlorocebus aethiops
Immunity, Innate
Porcine epidemic diarrhea virus*
RNA, Small Interfering / genetics
Signal Transduction
Swine
Vero Cells

Substances

RNA, Small Interfering
Adaptor Proteins, Vesicular Transport

Grants and funding

This research was partly funded by the National Natural Science Foundation of China grant number [32172867; 32202818], the 111 Project grant number [D18007] and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).