Faculty, Staff and Student Publications
Publication Date
7-18-2025
Journal
Cell Death & Disease
DOI
10.1038/s41419-025-07838-z
PMID
40681530
PMCID
PMC12274286
PubMedCentral® Posted Date
7-18-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Type I interferons are secreted in response to various stimuli and are used as a treatment for many diseases, including infections with the hepatitis B virus (HBV) and its satellite virus, hepatitis delta (HDV). HDV significantly aggravates HBV-mediated liver damage and is - in contrast to HBV - a strong inducer of interferon responses, including IFN-β. As the role of IFN- β in liver metabolism is so far ill explored, we studied its impact on hepatocyte metabolism in HDV-infected cultures. Transcriptome analysis, isotope tracing and functional tests on differentiated, HDV-infected hepatocytes showed reduction of mitochondrial TCA cycle and respiratory activity and increases in serine, asparagine and glutathione synthesis. Furthermore, the stress-response factor ATF4 was activated by IFN-β via yet unidentified non-canonical mechanisms and mediated resistance to oxidants. IFN-β furthermore reduced the expression and activity of liver differentiation markers. Thus, IFN-β-mediated dedifferentiation and stress-resistance may contribute to HDV-associated liver pathology.
Keywords
Hepatocytes, Oxidative Stress, Interferon-beta, Humans, Hepatitis Delta Virus, Cells, Cultured, Mitochondria, Activating Transcription Factor 4
Published Open-Access
yes
Recommended Citation
Khomich, Olga A; Giavalisco, Patrick; Parent, Romain; et al., "Ifn-β Production Promotes Metabolic Rewiring and Protection Against Oxidative Stress in Hepatitis Delta Virus-Infected Hepatocyte Cultures" (2025). Faculty, Staff and Student Publications. 4454.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4454
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