| Autor: |
Juan Li, Mingshu Wang, Shan Zhou, Anchun Cheng, Xuming Ou, Di Sun, Ying Wu, Qiao Yang, Qun Gao, Juan Huang, Bin Tian, Sai Mao, Shaqiu Zhang, Xinxin Zhao, Renyong Jia, Mafeng Liu, Dekang Zhu, Shun Chen, Yunya Liu, Yanling Yu, Ling Zhang, Leichang Pan |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Veterinary Research, Vol 53, Iss 1, Pp 1-11 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1297-9716 |
| DOI: |
10.1186/s13567-022-01081-6 |
| Popis: |
Abstract Duck hepatitis A virus type 1 (DHAV-1) is one of the main pathogens responsible for death in ducklings. Autophagy is a catabolic process that maintains cellular homeostasis, and the PI3KC3 protein plays an important role in the initiation of autophagy. DHAV-1 infection induces autophagy in duck embryo fibroblasts (DEFs) but the molecular mechanism between it and autophagy has not been reported. First, we determined that DHAV-1 infection induces autophagy in DEFs and that autophagy induction is dependent on the integrity of viral proteins by infecting DEFs with UV-inactivated or heat-inactivated DHAV-1. Then, in experiments using the pharmacological autophagy inducer rapamycin and the autophagy inhibitor chloroquine, autophagy inhibition was shown to reduce intracellular and extracellular DHAV-1 genome copies and viral titres. These results suggest that autophagy activated by DHAV-1 infection in DEFs affects DHAV-1 proliferation and extracellular release. Next, we screened the autophagy-inducing effects of the DHAV-1 structural proteins VP0, VP3, and VP1 and found that all DHAV-1 structural proteins could induce autophagy in DEFs but not the full autophagic flux. Finally, we found that VP1 promotes protein expression of PI3KC3 and Beclin1 by western blot experiments and that VP1 interacts with PI3KC3 by co-immunoprecipitation experiments; moreover, 3-MA-induced knockdown of PI3KC3 inhibited VP1 protein-induced autophagy in DEFs. In conclusion, the DHAV-1 structural protein VP1 regulates the PI3KC3 complex by interacting with PI3KC3 to induce autophagy in DEFs. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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