Multimodal characterization of the responsiveness of eight hepatitis D virus genotype isolates to interferon-alpha treatment
Chronic hepatitis delta virus (HDV) infection represents the most severe form of viral hepatitis. This study comprehensively evaluated the antiviral efficacy of interferon-alpha (IFN-α) subtypes across eight HDV genotypes during <i>de novo</i> infection, cell mitosis, or in quiescent cells. Herein, we found that IFN-α exhibits potent but varied efficiency against HDV 1-8 isolates upon <i>de novo</i> infection and cell mitosis. Conversely, HDVs in resting cells are resistant to IFN-α subtypes, regardless of the cellular ADAR1 levels. Among different subtypes, IFN-α2a, IFN-α10, and IFN-α14 exhibit the strongest anti-HDV activity and synergize with bulevirtide in suppressing HDV replication. These findings provide crucial insights into the optimization of IFN-based monotherapy and combinational therapy against chronic HDV infection.
Authors
- Chengqian Feng
- Hongbo Guo (ORCID: https://orcid.org/0009-0006-9241-1414)
- Xiaoting Ding (ORCID: https://orcid.org/0000-0002-7290-1452)
- Zhanghao Feng
- Wenshi Wang (ORCID: https://orcid.org/0000-0002-7330-262X)
- Qiudi Li (ORCID: https://orcid.org/0009-0003-5180-9053)
- Mei Liu (ORCID: https://orcid.org/0009-0007-5448-9795)
- Qili Yao (ORCID: https://orcid.org/0000-0002-1639-5911)
- Shijie Liang (ORCID: https://orcid.org/0000-0003-0890-7435)
- Stephan Urban (ORCID: https://orcid.org/0000-0003-1560-8038)
- Ying Li (ORCID: https://orcid.org/0000-0001-9513-843X)
- Feng Li (ORCID: https://orcid.org/0000-0003-3169-6349)
- Zhenfeng Zhang (ORCID: https://orcid.org/0000-0002-0013-3685)
- Yibo Ding (ORCID: https://orcid.org/0000-0002-2544-3882)
- Huiyuan Fu
- Yiwen Sha
- R. Si
Institutions
- Xuzhou Medical College (CN)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Southern University of Science and Technology (CN)
- Shanghai Public Health Clinical Center (CN)
- German Center for Infection Research (DE)
- Guangzhou Eighth People's Hospital (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Journal of Virology
- Published
- 2025-09-18
- DOI
- https://doi.org/10.1128/jvi.01280-25
- Citations
- 1
- Primary Topic
- Hepatitis C virus research
- Type
- article
- Field-Weighted Citation Impact
- 1.32