Host Factor SRSF7 Promotes HBV Replication Through Binding to and Stabilising Viral pgRNA

Area of Science:

• Virology
• Molecular Biology
• Hepatology

Background:

• Hepatitis B virus (HBV) causes chronic hepatitis B (CHB), a significant global health concern.
• The HBV pregenomic RNA (pgRNA) is crucial for viral replication and nucleocapsid assembly.
• The role of host factor serine/arginine (SR)-rich splicing factor 7 (SRSF7) in HBV pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the biological function and regulatory mechanisms of SRSF7 in HBV replication.
• To elucidate how SRSF7 influences HBV RNA levels and stability.
• To explore the potential of SRSF7 as a therapeutic target for CHB.

Main Methods:

• Utilized HBV replication models in various cell lines to assess SRSF7's impact.
• Employed knockdown and overexpression techniques to manipulate SRSF7 levels.
• Analyzed HBV RNA stability and SRSF7 binding to pgRNA, including the epsilon (ε) element.

Main Results:

• SRSF7 significantly promotes HBV replication and increases HBV RNA levels.
• SRSF7 enhances HBV RNA stability post-transcriptionally, independent of splicing regulation.
• SRSF7 directly binds to pgRNA, with binding affinity dependent on the ε element's structural integrity.

Conclusions:

• Host factor SRSF7 plays a critical role in promoting HBV replication.
• SRSF7 stabilizes HBV RNA, contributing to increased viral load.
• These findings highlight novel HBV-host interactions and suggest SRSF7 as a potential target for anti-HBV drug development.