Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 5 min ago
Peer-reviewedCC BY 4.0mBio

Resolution of viral R-loop by DHX9 promotes hepatitis B virus replication

  • Yubo Pi1
  • Huimin Luo1,2
  • Kai Wang1
  • Ni Tang1
  • Ailong Huang1
  • Yanmeng Chen3
  1. 1Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
  2. 2Youyang Hospital, a Branch of The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  3. 3Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China
Read full textDOICite

Abstract

Hepatitis B virus (HBV) is a hepatotropic DNA virus with a compact 3.2 kb genome that replicates via reverse transcription. HBV covalently closed circular DNA (cccDNA) transcription shares molecular features with R-loop. DExH-box helicase 9 (DHX9) has been shown to be associated with R-loop accumulation, genome instability, and HBV replication. However, the role of DHX9-mediated R-loop homeostasis in HBV transcription has not yet been elucidated. In this study, we identified a critical role of DHX9 in resolving R-loops at transcription termination during HBV transcription. We demonstrate that HBV replication promotes viral R-loop accumulation. DHX9 promotes HBV R-loop resolution, HBV cccDNA transcription termination, and subsequent nuclear export of the 3.5 kb HBV RNA, facilitating HBV DNA replication. These findings reveal DHX9-mediated R-loop resolution as a potential therapeutic target for antiviral intervention.

IMPORTANCE: The persistence of HBV cccDNA poses a major challenge to achieving a cure for chronic hepatitis B. While R-loop structures have been implicated in the life cycles of viruses, their formation and functional significance in HBV replication have remained largely unexplored. This study provides the first evidence that the cellular helicase DHX9 resolves transcription-replication conflicts by dissolving R-loops formed during HBV replication. Our findings also identify DHX9-mediated R-loop resolution as a critical mechanism supporting the HBV life cycle. Consequently, targeting DHX9 presents a promising therapeutic strategy to silence the persistent HBV cccDNA reservoir.

Related

  1. HMGB1 Protein Binds to Influenza Virus Nucleoprotein and Promotes Viral Replication
    Dorothée Moisy, Sergiy Avilov, Yves Jacob +5
    Journal of VirologyPeer-reviewedLicence not stated115 citedEpidemiology & public healthHAL
  2. Hepatitis A Virus (HAV) Recurrence and De Novo Hepatitis A Acquired at Time of Liver Transplantation: Comparison of Graft HAV Infection and Viral Kinetics
    David Mutimer, Elinor Latham, Sowsan F. Atabani +1
    Journal of viral hepatitisPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  3. Myristylation of the Hepatitis B Virus Large Surface Protein Is Essential for Viral Infectivity
    P. Gripon, J. Le Seyec, S. Rumin +1
    VirologyPeer-reviewedLicence not stated197 citedEpidemiology & public healthHAL
  4. Antiviral Sesquiterpene Lactones from Laurus nobilis L.: Inhibition of Hepatitis C Virus and Dengue Virus Replication.
    Yhiya Amen, Marwa Elsbaey, George Mpekoulis +5
    VirusesPeer-reviewedCC BYFull textOncologyEurope PMC
  5. A Transfusion-transmitted Chronic Hepatitis E Virus Infection after Allogeneic Bone Marrow Transplantation with Viral Clearance Following Immunosuppression Tapering
    Keijiro Sato, Hiroko Kazumoto, Ami Tanaka +6
    Internal MedicinePeer-reviewedCC BY-NC-NDFull text1 citedGeneral medicineJ-STAGE

Cite

BibTeXRIS
BibTeX
@article{pi2026resolution,
  title = {{Resolution of viral R-loop by DHX9 promotes hepatitis B virus replication}},
  author = {Yubo Pi and Huimin Luo and Kai Wang and Ni Tang and Ailong Huang and Yanmeng Chen},
  journal = {mBio},
  year = {2026},
  month = sep,
  doi = {10.1128/mbio.01449-26},
  url = {https://doi.org/10.1128/mbio.01449-26},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Resolution of viral R-loop by DHX9 promotes hepatitis B virus replication
AU  - Yubo Pi
AU  - Huimin Luo
AU  - Kai Wang
AU  - Ni Tang
AU  - Ailong Huang
AU  - Yanmeng Chen
PY  - 2026
DA  - 2026/09/18
JO  - mBio
DO  - 10.1128/mbio.01449-26
UR  - https://doi.org/10.1128/mbio.01449-26
AB  - Hepatitis B virus (HBV) is a hepatotropic DNA virus with a compact 3.2 kb genome that replicates via reverse transcription. HBV covalently closed circular DNA (cccDNA) transcription shares molecular features with R-loop. DExH-box helicase 9 (DHX9) has been shown to be associated with R-loop accumulation, genome instability, and HBV replication. However, the role of DHX9-mediated R-loop homeostasis in HBV transcription has not yet been elucidated. In this study, we identified a critical role of DHX9 in resolving R-loops at transcription termination during HBV transcription. We demonstrate that HBV replication promotes viral R-loop accumulation. DHX9 promotes HBV R-loop resolution, HBV cccDNA transcription termination, and subsequent nuclear export of the 3.5 kb HBV RNA, facilitating HBV DNA replication. These findings reveal DHX9-mediated R-loop resolution as a potential therapeutic target for antiviral intervention.  IMPORTANCE: The persistence of HBV cccDNA poses a major challenge to achieving a cure for chronic hepatitis B. While R-loop structures have been implicated in the life cycles of viruses, their formation and functional significance in HBV replication have remained largely unexplored. This study provides the first evidence that the cellular helicase DHX9 resolves transcription-replication conflicts by dissolving R-loops formed during HBV replication. Our findings also identify DHX9-mediated R-loop resolution as a critical mechanism supporting the HBV life cycle. Consequently, targeting DHX9 presents a promising therapeutic strategy to silence the persistent HBV cccDNA reservoir.
SN  - 2150-7511
ER  -