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Porcine Epidemic Diarrhea Virus Membrane Protein Interacted with IRF7 to Inhibit Type I IFN Production during Viral Infection
- Source :
- The Journal of Immunology. 206:2909-2923
- Publication Year :
- 2021
- Publisher :
- The American Association of Immunologists, 2021.
-
Abstract
- Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic porcine enteropathogenic coronavirus causing severe enteritis and lethal watery diarrhea in piglets. PEDV infection suppresses the synthesis of type I IFN, and multiple viral proteins of PEDV have been shown to target the adaptors of innate immune pathways to inhibit type I IFN production. In this study, we identified PEDV membrane (M) protein as a new antagonist of type I IFN production in both human embryonic kidney HEK293T cells and porcine kidney PK-15 cells and determined the antagonistic mechanism used by M protein to target IFN regulatory factor 7 (IRF7), an important regulator of type I IFN production. IRF7 is phosphorylated and activated by TBK1 and IKKε in response to viral infection. We found that PEDV M protein interacted with the inhibitory domain of IRF7 and significantly suppressed TBK1/IKKε-induced IRF7 phosphorylation and dimerization of IRF7, leading to the decreased expression of type I IFN, although it did not affect the interaction between TBK1/IKKε and IRF7. As expected, overexpression of M protein significantly increased PEDV replication in porcine cells. The M proteins of both epidemic PEDV strains and vaccine strain showed similar antagonistic effect on type I IFN production, and the 1-55 region of M protein was essential for disruption of IRF7 function by interacting with IRF7. Taken together, our data identified a new, to our knowledge, IFN antagonist of PEDV, as well as a novel, to our knowledge, antagonistic mechanism evolved by PEDV to inhibit type I IFN production.
- Subjects :
- Swine
Myeloma protein
Interferon Regulatory Factor-7
Immunology
medicine.disease_cause
Cell Line
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Humans
Immunology and Allergy
Coronavirus
Swine Diseases
Innate immune system
biology
Porcine epidemic diarrhea virus
HEK 293 cells
Membrane Proteins
biology.organism_classification
Virology
Membrane protein
Interferon Type I
Phosphorylation
IRF7
Coronavirus Infections
030215 immunology
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 206
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....0841051a1c79c37ad5597bfd44d0df05