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Updated: Jul 10, 2025
04:23
A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
6.6K
USP18 enhances dengue virus replication by regulating mitochondrial DNA release
Jenn-Haung Lai1, De-Wei Wu2, Chien-Hsiang Wu2
1Department of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Lin-Kou, Tao-Yuan, Taiwan, ROC. laiandho@gmail.com.
Scientific Reports
|November 18, 2023
Summary
Dengue virus (DENV) evades the immune system using USP18. This study reveals USP18 regulates DENV replication through both interferon-dependent and independent mitochondrial pathways, impacting viral spread.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Dengue virus (DENV) poses a significant global health challenge.
- Ubiquitin-specific protease 18 (USP18) aids DENV immune evasion by maintaining anti-interferon (IFN) effects.
- The precise mechanisms of USP18 in regulating DENV replication are not fully understood.
Purpose of the Study:
- To investigate the multifaceted roles of USP18 in DENV replication.
- To determine if USP18's regulation of DENV replication extends beyond IFN hyporesponsiveness.
- To elucidate the specific mitochondrial pathways involved in USP18-mediated DENV replication control.
Main Methods:
- Utilized IFN signaling blockade strategies: IFN neutralizing antibodies, anti-IFN receptor antibodies, Janus kinase inhibitors, and IFNAR1 knockout cells.
- Investigated USP18 localization within mitochondria.
- Analyzed mechanisms of mitochondrial dysfunction including ROS production, membrane potential changes, calcium mobilization, OGG1 expression, mtDNA oxidation/fragmentation, and mPTP opening.
Main Results:
- USP18 influences DENV replication through both IFN-associated and IFN-unassociated pathways.
- USP18 localized in mitochondria regulates the release of mitochondrial DNA (mtDNA) into the cytosol.
- Several mitochondrial factors, including mtROS, membrane potential, calcium flux, OGG1, mtDNA integrity, and mPTP, are implicated in USP18-controlled mtDNA release.
Conclusions:
- USP18 plays a dual role in regulating DENV replication, impacting both IFN responses and mitochondrial integrity.
- Mitochondrial pathways, particularly mtDNA release regulated by USP18, are critical in controlling DENV replication.
- This study identifies key mitochondrial components regulated by USP18 that influence DENV replication and its interplay with IFN signaling.
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