IFN-β production promotes metabolic rewiring and protection against oxidative stress in hepatitis delta virus-infected hepatocyte cultures
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-07-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07838-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849388736213680128 |
|---|---|
| author | Olga A. Khomich Patrick Giavalisco Romain Parent George S. Krasnov Peter Tessarz Philip Meuleman Rani Burm Natalia F. Zakirova Jennifer Molle Enkhtuul Batbold Eyal Gottlieb Fabien Zoulim Alexander V. Ivanov Birke Bartosch |
| author_facet | Olga A. Khomich Patrick Giavalisco Romain Parent George S. Krasnov Peter Tessarz Philip Meuleman Rani Burm Natalia F. Zakirova Jennifer Molle Enkhtuul Batbold Eyal Gottlieb Fabien Zoulim Alexander V. Ivanov Birke Bartosch |
| author_sort | Olga A. Khomich |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e0834e74c6304b2c923c409d0041ad63 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-e0834e74c6304b2c923c409d0041ad632025-08-20T03:42:10ZengNature Publishing GroupCell Death and Disease2041-48892025-07-0116111110.1038/s41419-025-07838-zIFN-β production promotes metabolic rewiring and protection against oxidative stress in hepatitis delta virus-infected hepatocyte culturesOlga A. Khomich0Patrick Giavalisco1Romain Parent2George S. Krasnov3Peter Tessarz4Philip Meuleman5Rani Burm6Natalia F. Zakirova7Jennifer Molle8Enkhtuul Batbold9Eyal Gottlieb10Fabien Zoulim11Alexander V. Ivanov12Birke Bartosch13Lyon Hepatology Institute; INSERM Unit 1350 PaThLiv; Université Claude Bernard Lyon 1Max Planck Institute for Biology of AgeingLyon Hepatology Institute; INSERM Unit 1350 PaThLiv; Université Claude Bernard Lyon 1Engelhardt Institute of Molecular Biology, Russian Academy of SciencesDepartment of Human Biology, Radboud Institute for Molecular Life Sciences, Faculty of Science, Radboud UniversityLaboratory of Liver Infectious Diseases, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent UniversityLaboratory of Liver Infectious Diseases, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent UniversityEngelhardt Institute of Molecular Biology, Russian Academy of SciencesLyon Hepatology Institute; INSERM Unit 1350 PaThLiv; Université Claude Bernard Lyon 1Lyon Hepatology Institute; INSERM Unit 1350 PaThLiv; Université Claude Bernard Lyon 1Department of Cancer Biology, University of Texas MD Anderson Cancer CenterLyon Hepatology Institute; INSERM Unit 1350 PaThLiv; Université Claude Bernard Lyon 1Engelhardt Institute of Molecular Biology, Russian Academy of SciencesLyon Hepatology Institute; INSERM Unit 1350 PaThLiv; Université Claude Bernard Lyon 1Abstract 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.https://doi.org/10.1038/s41419-025-07838-z |
| spellingShingle | Olga A. Khomich Patrick Giavalisco Romain Parent George S. Krasnov Peter Tessarz Philip Meuleman Rani Burm Natalia F. Zakirova Jennifer Molle Enkhtuul Batbold Eyal Gottlieb Fabien Zoulim Alexander V. Ivanov Birke Bartosch IFN-β production promotes metabolic rewiring and protection against oxidative stress in hepatitis delta virus-infected hepatocyte cultures Cell Death and Disease |
| title | IFN-β production promotes metabolic rewiring and protection against oxidative stress in hepatitis delta virus-infected hepatocyte cultures |
| title_full | IFN-β production promotes metabolic rewiring and protection against oxidative stress in hepatitis delta virus-infected hepatocyte cultures |
| title_fullStr | IFN-β production promotes metabolic rewiring and protection against oxidative stress in hepatitis delta virus-infected hepatocyte cultures |
| title_full_unstemmed | IFN-β production promotes metabolic rewiring and protection against oxidative stress in hepatitis delta virus-infected hepatocyte cultures |
| title_short | IFN-β production promotes metabolic rewiring and protection against oxidative stress in hepatitis delta virus-infected hepatocyte cultures |
| title_sort | ifn β production promotes metabolic rewiring and protection against oxidative stress in hepatitis delta virus infected hepatocyte cultures |
| url | https://doi.org/10.1038/s41419-025-07838-z |
| work_keys_str_mv | AT olgaakhomich ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT patrickgiavalisco ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT romainparent ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT georgeskrasnov ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT petertessarz ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT philipmeuleman ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT raniburm ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT nataliafzakirova ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT jennifermolle ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT enkhtuulbatbold ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT eyalgottlieb ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT fabienzoulim ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT alexandervivanov ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures AT birkebartosch ifnbproductionpromotesmetabolicrewiringandprotectionagainstoxidativestressinhepatitisdeltavirusinfectedhepatocytecultures |