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Hepatitis D virus-induced interferon response and administered interferons control cell division-mediated virus
Zhenfeng Zhang1, Yi Ni1, Florian A Lempp1
1Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Journal of Hepatology
|May 31, 2022
Summary
Interferon (IFN) effectively suppresses Hepatitis D Virus (HDV) spread through cell division, a key factor in viral persistence. This discovery offers new therapeutic strategies for chronic Hepatitis D by targeting cell division-mediated viral transmission.
Area of Science:
- Hepatology and Virology
- Immunology
- Cell Biology
Background:
- Chronic hepatitis D (HDV) poses a significant global health challenge.
- HDV persistence is driven by both de novo infection and cell division-mediated spread.
- Existing antivirals targeting de novo infection are less effective against cell division-mediated spread.
Purpose of the Study:
- To investigate the impact of interferon (IFN) response on cell division-mediated HDV spread.
- To elucidate the mechanism by which IFNs affect HDV transmission.
- To identify potential synergistic therapeutic strategies for chronic hepatitis D.
Main Methods:
- Utilized cell culture models of HDV infection, including IFN-defective and IFN-competent cell lines.
- Manipulated IFN response by blocking endogenous IFN activation and applying exogenous IFN treatments.
- Assessed HDV spread efficiency in dividing versus resting cells under various experimental conditions.
Main Results:
- Cell division-mediated HDV spread was significantly restricted in IFN-competent cells compared to IFN-defective cells.
- Exogenous IFN-α/-λ1 treatment inhibited HDV spread in dividing cells but had minimal effect on replication in resting cells.
- Blocking endogenous IFN response or using JAK1/2 inhibitors augmented HDV spread, indicating a crucial role for IFN in controlling cell division-mediated transmission.
- IFN response accelerated HDV RNA decay in dividing cells.
Conclusions:
- Both endogenous and exogenous IFNs suppress cell division-mediated HDV spread, primarily by accelerating HDV RNA decay.
- This study reveals a novel mode-of-action for IFNs in controlling HDV transmission.
- Findings support the rationale for combination therapies, explaining the enhanced efficacy of IFN in patients with lower viral loads and guiding future treatment development.
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