The DHAV-1 protein VP1 interacts with PI3KC3 to induce autophagy through the PI3KC3 complex
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-08-01
|
| Series: | Veterinary Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13567-022-01081-6 |
| _version_ | 1811340313933905920 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Juan Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T18:40:06Z |
| format | Article |
| id | doaj.art-b3d357d26b6d445789e23b33f1fcebe5 |
| institution | Directory Open Access Journal |
| issn | 1297-9716 |
| language | English |
| last_indexed | 2024-04-13T18:40:06Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj.art-b3d357d26b6d445789e23b33f1fcebe52022-12-22T02:34:46ZengBMCVeterinary Research1297-97162022-08-0153111110.1186/s13567-022-01081-6The DHAV-1 protein VP1 interacts with PI3KC3 to induce autophagy through the PI3KC3 complexJuan Li0Mingshu Wang1Shan Zhou2Anchun Cheng3Xuming Ou4Di Sun5Ying Wu6Qiao Yang7Qun Gao8Juan Huang9Bin Tian10Sai Mao11Shaqiu Zhang12Xinxin Zhao13Renyong Jia14Mafeng Liu15Dekang Zhu16Shun Chen17Yunya Liu18Yanling Yu19Ling Zhang20Leichang Pan21Institute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityKey Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityInstitute of Preventive Veterinary Medicine, Sichuan Agricultural UniversityAbstract 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.https://doi.org/10.1186/s13567-022-01081-6Duck hepatitis A virus type 1VP1autophagyPI3KC3Beclin1 |
| spellingShingle | 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 The DHAV-1 protein VP1 interacts with PI3KC3 to induce autophagy through the PI3KC3 complex Veterinary Research Duck hepatitis A virus type 1 VP1 autophagy PI3KC3 Beclin1 |
| title | The DHAV-1 protein VP1 interacts with PI3KC3 to induce autophagy through the PI3KC3 complex |
| title_full | The DHAV-1 protein VP1 interacts with PI3KC3 to induce autophagy through the PI3KC3 complex |
| title_fullStr | The DHAV-1 protein VP1 interacts with PI3KC3 to induce autophagy through the PI3KC3 complex |
| title_full_unstemmed | The DHAV-1 protein VP1 interacts with PI3KC3 to induce autophagy through the PI3KC3 complex |
| title_short | The DHAV-1 protein VP1 interacts with PI3KC3 to induce autophagy through the PI3KC3 complex |
| title_sort | dhav 1 protein vp1 interacts with pi3kc3 to induce autophagy through the pi3kc3 complex |
| topic | Duck hepatitis A virus type 1 VP1 autophagy PI3KC3 Beclin1 |
| url | https://doi.org/10.1186/s13567-022-01081-6 |
| work_keys_str_mv | AT juanli thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT mingshuwang thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT shanzhou thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT anchuncheng thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT xumingou thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT disun thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT yingwu thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT qiaoyang thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT qungao thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT juanhuang thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT bintian thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT saimao thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT shaqiuzhang thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT xinxinzhao thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT renyongjia thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT mafengliu thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT dekangzhu thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT shunchen thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT yunyaliu thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT yanlingyu thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT lingzhang thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT leichangpan thedhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT juanli dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT mingshuwang dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT shanzhou dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT anchuncheng dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT xumingou dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT disun dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT yingwu dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT qiaoyang dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT qungao dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT juanhuang dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT bintian dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT saimao dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT shaqiuzhang dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT xinxinzhao dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT renyongjia dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT mafengliu dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT dekangzhu dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT shunchen dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT yunyaliu dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT yanlingyu dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT lingzhang dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex AT leichangpan dhav1proteinvp1interactswithpi3kc3toinduceautophagythroughthepi3kc3complex |