Porcine epidemic diarrhoea virus (PEDV) infection activates AMPK and JNK through TAK1 to induce autophagy and enhance virus replication
Autophagy plays an important role in defending against invading microbes. However, numerous viruses can subvert autophagy to benefit their replication. Porcine epidemic diarrhoea virus (PEDV) is an aetiological agent that causes severe porcine epidemic diarrhoea. How PEDV infection regulates autopha...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Virulence |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2022.2127192 |
| _version_ | 1798000403010289664 |
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| author | Jingxiang Wang Xianjin Kan Xiaomei Li Jing Sun Xiulong Xu |
| author_facet | Jingxiang Wang Xianjin Kan Xiaomei Li Jing Sun Xiulong Xu |
| author_sort | Jingxiang Wang |
| collection | DOAJ |
| description | Autophagy plays an important role in defending against invading microbes. However, numerous viruses can subvert autophagy to benefit their replication. Porcine epidemic diarrhoea virus (PEDV) is an aetiological agent that causes severe porcine epidemic diarrhoea. How PEDV infection regulates autophagy and its role in PEDV replication are inadequately understood. Herein, we report that PEDV induced complete autophagy in Vero and IPEC-DQ cells, as evidenced by increased LC3 lipidation, p62 degradation, and the formation of autolysosomes. The lysosomal protease inhibitors chloroquine (CQ) or bafilomycin A and Beclin-1 or ATG5 knockdown blocked autophagic flux and inhibited PEDV replication. PEDV infection activated AMP-activated protein kinase (AMPK) and c-Jun terminal kinase (JNK) by activating TGF-beta-activated kinase 1 (TAK1). Compound C (CC), an AMPK inhibitor, and SP600125, a JNK inhibitor, inhibited PEDV-induced autophagy and virus replication. AMPK activation led to increased ULK1S777 phosphorylation and activation. Inhibition of ULK1 activity by SBI-0206965 (SBI) and TAK1 activity by 5Z-7-Oxozeaenol (5Z) or by TAK1 siRNA led to the suppression of autophagy and virus replication. Our study provides mechanistic insights into PEDV-induced autophagy and how PEDV infection leads to JNK and AMPK activation. |
| first_indexed | 2024-04-11T11:19:40Z |
| format | Article |
| id | doaj.art-a5e347a229734f60837d4432fe3c365e |
| institution | Directory Open Access Journal |
| issn | 2150-5594 2150-5608 |
| language | English |
| last_indexed | 2024-04-11T11:19:40Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj.art-a5e347a229734f60837d4432fe3c365e2022-12-22T04:27:06ZengTaylor & Francis GroupVirulence2150-55942150-56082022-12-011311697171210.1080/21505594.2022.2127192Porcine epidemic diarrhoea virus (PEDV) infection activates AMPK and JNK through TAK1 to induce autophagy and enhance virus replicationJingxiang Wang0Xianjin Kan1Xiaomei Li2Jing Sun3Xiulong Xu4College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, P. R. ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, P. R. ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, P. R. ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, P. R. ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, P. R. ChinaAutophagy plays an important role in defending against invading microbes. However, numerous viruses can subvert autophagy to benefit their replication. Porcine epidemic diarrhoea virus (PEDV) is an aetiological agent that causes severe porcine epidemic diarrhoea. How PEDV infection regulates autophagy and its role in PEDV replication are inadequately understood. Herein, we report that PEDV induced complete autophagy in Vero and IPEC-DQ cells, as evidenced by increased LC3 lipidation, p62 degradation, and the formation of autolysosomes. The lysosomal protease inhibitors chloroquine (CQ) or bafilomycin A and Beclin-1 or ATG5 knockdown blocked autophagic flux and inhibited PEDV replication. PEDV infection activated AMP-activated protein kinase (AMPK) and c-Jun terminal kinase (JNK) by activating TGF-beta-activated kinase 1 (TAK1). Compound C (CC), an AMPK inhibitor, and SP600125, a JNK inhibitor, inhibited PEDV-induced autophagy and virus replication. AMPK activation led to increased ULK1S777 phosphorylation and activation. Inhibition of ULK1 activity by SBI-0206965 (SBI) and TAK1 activity by 5Z-7-Oxozeaenol (5Z) or by TAK1 siRNA led to the suppression of autophagy and virus replication. Our study provides mechanistic insights into PEDV-induced autophagy and how PEDV infection leads to JNK and AMPK activation.https://www.tandfonline.com/doi/10.1080/21505594.2022.2127192Porcine epidemic diarrhoea virusautophagyTAK1AMPKJNK |
| spellingShingle | Jingxiang Wang Xianjin Kan Xiaomei Li Jing Sun Xiulong Xu Porcine epidemic diarrhoea virus (PEDV) infection activates AMPK and JNK through TAK1 to induce autophagy and enhance virus replication Virulence Porcine epidemic diarrhoea virus autophagy TAK1 AMPK JNK |
| title | Porcine epidemic diarrhoea virus (PEDV) infection activates AMPK and JNK through TAK1 to induce autophagy and enhance virus replication |
| title_full | Porcine epidemic diarrhoea virus (PEDV) infection activates AMPK and JNK through TAK1 to induce autophagy and enhance virus replication |
| title_fullStr | Porcine epidemic diarrhoea virus (PEDV) infection activates AMPK and JNK through TAK1 to induce autophagy and enhance virus replication |
| title_full_unstemmed | Porcine epidemic diarrhoea virus (PEDV) infection activates AMPK and JNK through TAK1 to induce autophagy and enhance virus replication |
| title_short | Porcine epidemic diarrhoea virus (PEDV) infection activates AMPK and JNK through TAK1 to induce autophagy and enhance virus replication |
| title_sort | porcine epidemic diarrhoea virus pedv infection activates ampk and jnk through tak1 to induce autophagy and enhance virus replication |
| topic | Porcine epidemic diarrhoea virus autophagy TAK1 AMPK JNK |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2022.2127192 |
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