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The host gene CSTF2 regulates HBV replication via HBV PRE-induced nuclear export
Jinyu Wang1, Jing Li2, Wentao Xie1
1Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Acta Biochimica Et Biophysica Sinica
|December 26, 2024
Summary
Host gene CSTF2 (cleavage stimulation factor subunit 2) influences hepatitis B virus (HBV) replication. Upregulated CSTF2 expression correlates with viral control, suggesting CSTF2 as a therapeutic target for HBV infection.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Hepatitis B virus (HBV) infection remains a significant global health challenge.
- Understanding host factors that regulate HBV replication is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the role of the host gene cleavage stimulation factor subunit 2 (CSTF2) in regulating hepatitis B virus (HBV) replication dynamics.
- To explore the potential of CSTF2 as a therapeutic target for HBV infection.
Main Methods:
- Analysis of CSTF2 gene expression across different phases of HBV infection.
- Overexpression of CSTF2 in HBV-infected cells to assess its impact on viral markers (DNA, RNA, proteins).
- Investigation of CSTF2 subcellular localization and interaction with HBV posttranscriptional regulatory element (PRE) upon HBV transfection.
Main Results:
- CSTF2 expression is upregulated in immune-reactive and inactive HBV carrier states compared to the immune-tolerant phase.
- CSTF2 overexpression leads to a dose-dependent reduction in HBV DNA and viral protein levels, while HBV RNA levels remain unchanged.
- HBV transfection induces CSTF2 relocalization to the cytoplasm, potentially via interaction with HBV PRE, inhibiting HBV RNA nuclear export.
- Specific functional domains of CSTF2 exhibit distinct antiviral activities.
Conclusions:
- CSTF2 plays a significant role in controlling HBV replication through multifaceted host defense mechanisms.
- The interaction between CSTF2 and HBV PRE impacts viral RNA nuclear export.
- CSTF2 represents a promising candidate for novel antiviral therapeutic strategies against HBV.
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