Interferon Alpha Induces Cellular Autophagy and Modulates Hepatitis B Virus Replication.

Publisher: Frontiers Media SA Country of Publication: Switzerland NLM ID: 101585359 Publication Model: eCollection Cited Medium: Internet ISSN: 2235-2988 (Electronic) Linking ISSN: 22352988 NLM ISO Abbreviation: Front Cell Infect Microbiol Subsets: MEDLINE

Original Publication: Lausanne : Frontiers Media SA

Hepatitis B*/drug therapy ; Hepatitis B virus*/drug effects ; Hepatitis B virus*/physiology ; Interferon-alpha*/pharmacology ; Virus Replication*/drug effects; Autophagy ; Humans

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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Li, Kemper, Broering, Chen, Yuan, Wang and Lu.)

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Keywords: AMPK; Akt/mTOR signaling; Hepatitis B virus; IFNα-2a; autophagy

0 (Interferon-alpha)

Date Created: 20220221 Date Completed: 20220406 Latest Revision: 20220531

20240105

PMC8847603

10.3389/fcimb.2022.804011

35186790