Interferon Alpha Induces Cellular Autophagy and Modulates Hepatitis B Virus Replication
Hepatitis B virus (HBV) infection causes acute and chronic liver diseases, including severe hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Interferon alpha 2a (IFNα-2a) is commonly used for treating chronic HBV infection. However, its efficacy remains relatively low. Yet, the immuno...
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| Format: | Article |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.804011/full |
| _version_ | 1818324429992624128 |
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| author | Jia Li Thekla Kemper Ruth Broering Jieliang Chen Zhenghong Yuan Xueyu Wang Xueyu Wang Mengji Lu |
| author_facet | Jia Li Thekla Kemper Ruth Broering Jieliang Chen Zhenghong Yuan Xueyu Wang Xueyu Wang Mengji Lu |
| author_sort | Jia Li |
| collection | DOAJ |
| description | Hepatitis B virus (HBV) infection causes acute and chronic liver diseases, including severe hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Interferon alpha 2a (IFNα-2a) is commonly used for treating chronic HBV infection. However, its efficacy remains relatively low. Yet, the immunological and molecular mechanisms for successful IFNα-2a treatment remain elusive. One issue is whether the application of increasing IFNα doses may modulate cellular processes and HBV replication in hepatic cells. In the present study, we focused on the interaction of IFNα signaling with other cellular signaling pathways and the consequence for HBV replication. The results showed that with the concentration of 6000 U/ml IFNα-2a treatment downregulated the activity of not only the Akt/mTOR signaling but also the AMPK signaling. Additionally, IFNα-2a treatment increased the formation of the autophagosomes by blocking autophagic degradation. Furthermore, IFNα-2a treatment inhibited the Akt/mTOR signaling and initiated autophagy under low and high glucose concentrations. In reverse, inhibition of autophagy using 3-methyladenine (3-MA) and glucose concentrations influenced the expression of IFNα-2a-induced ISG15 and IFITM1. Despite of ISGs induction, HBV replication and gene expression in HepG2.2.15 cells, a cell model with continuous HBV replication, were slightly increased at high doses of IFNα-2a. In conclusion, our study indicates that IFNα-2a treatment may interfere with multiple intracellular signaling pathways, facilitate autophagy initiation, and block autophagic degradation, thereby resulting in slightly enhanced HBV replication. |
| first_indexed | 2024-12-13T11:28:27Z |
| format | Article |
| id | doaj.art-d1a938296acf4a6dbc37dde35cc59df4 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-13T11:28:27Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-d1a938296acf4a6dbc37dde35cc59df42022-12-21T23:48:04ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-02-011210.3389/fcimb.2022.804011804011Interferon Alpha Induces Cellular Autophagy and Modulates Hepatitis B Virus ReplicationJia Li0Thekla Kemper1Ruth Broering2Jieliang Chen3Zhenghong Yuan4Xueyu Wang5Xueyu Wang6Mengji Lu7Insititute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInsititute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Gastroenterology, Hepatology and Transplant Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyKey Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaKey Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaInsititute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyState Key Laboratory for Diagnostic and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaInsititute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyHepatitis B virus (HBV) infection causes acute and chronic liver diseases, including severe hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Interferon alpha 2a (IFNα-2a) is commonly used for treating chronic HBV infection. However, its efficacy remains relatively low. Yet, the immunological and molecular mechanisms for successful IFNα-2a treatment remain elusive. One issue is whether the application of increasing IFNα doses may modulate cellular processes and HBV replication in hepatic cells. In the present study, we focused on the interaction of IFNα signaling with other cellular signaling pathways and the consequence for HBV replication. The results showed that with the concentration of 6000 U/ml IFNα-2a treatment downregulated the activity of not only the Akt/mTOR signaling but also the AMPK signaling. Additionally, IFNα-2a treatment increased the formation of the autophagosomes by blocking autophagic degradation. Furthermore, IFNα-2a treatment inhibited the Akt/mTOR signaling and initiated autophagy under low and high glucose concentrations. In reverse, inhibition of autophagy using 3-methyladenine (3-MA) and glucose concentrations influenced the expression of IFNα-2a-induced ISG15 and IFITM1. Despite of ISGs induction, HBV replication and gene expression in HepG2.2.15 cells, a cell model with continuous HBV replication, were slightly increased at high doses of IFNα-2a. In conclusion, our study indicates that IFNα-2a treatment may interfere with multiple intracellular signaling pathways, facilitate autophagy initiation, and block autophagic degradation, thereby resulting in slightly enhanced HBV replication.https://www.frontiersin.org/articles/10.3389/fcimb.2022.804011/fullHepatitis B virusIFNα-2aAkt/mTOR signalingAMPKautophagy |
| spellingShingle | Jia Li Thekla Kemper Ruth Broering Jieliang Chen Zhenghong Yuan Xueyu Wang Xueyu Wang Mengji Lu Interferon Alpha Induces Cellular Autophagy and Modulates Hepatitis B Virus Replication Frontiers in Cellular and Infection Microbiology Hepatitis B virus IFNα-2a Akt/mTOR signaling AMPK autophagy |
| title | Interferon Alpha Induces Cellular Autophagy and Modulates Hepatitis B Virus Replication |
| title_full | Interferon Alpha Induces Cellular Autophagy and Modulates Hepatitis B Virus Replication |
| title_fullStr | Interferon Alpha Induces Cellular Autophagy and Modulates Hepatitis B Virus Replication |
| title_full_unstemmed | Interferon Alpha Induces Cellular Autophagy and Modulates Hepatitis B Virus Replication |
| title_short | Interferon Alpha Induces Cellular Autophagy and Modulates Hepatitis B Virus Replication |
| title_sort | interferon alpha induces cellular autophagy and modulates hepatitis b virus replication |
| topic | Hepatitis B virus IFNα-2a Akt/mTOR signaling AMPK autophagy |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.804011/full |
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