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[HBx Protein Potentiates Hepatitis B Virus Reactivation].

S A Brezgin1,2, A P Kostyusheva1,3, N I Ponomareva1,2

  • 1Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases, Sechenov First Moscow State Medical University, Ministry of Healthcare of the Russian Federation (Sechenov University), Moscow, 119048 Russia.

Molekuliarnaia Biologiia
|September 27, 2022
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Summary

Hepatitis B virus (HBV) can reactivate from an inactive state, particularly when the HBx protein is altered. Certain treatments like doxorubicin and hydrogen peroxide can trigger HBV reactivation.

Keywords:
ATMATRChk1/2DNA damageHBV DNAanticancer therapiescccDNAcomorbiditiesviral load

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Area of Science:

  • Hepatology
  • Virology
  • Molecular Biology

Background:

  • Chronic Hepatitis B (HBV) affects over 250 million globally.
  • HBV reactivation can lead to severe liver complications and death.
  • Understanding HBV reactivation mechanisms is crucial for patient management.

Purpose of the Study:

  • To investigate the role of HBx protein in HBV reactivation.
  • To explore HBV reactivation from a transcriptionally silenced state.
  • To examine HBV reactivation induced by genotoxic and targeted therapies.

Main Methods:

  • Analysis of HBx protein effects on HBV replication.
  • Modeling HBV reactivation from a methylated, transcriptionally inactivated HBV genome.
  • Treatment of HBV models with doxorubicin, hydrogen peroxide, sunitinib, and bortezomib.

Main Results:

  • Wild-type and mutant HBx proteins potentiate HBV replication and reactivation.
  • HBV reactivation from a transcriptionally inactive state was demonstrated.
  • Doxorubicin and hydrogen peroxide induced HBV reactivation in both active and silenced viral genomes.
  • Sunitinib showed weak reactivation; bortezomib had no effect in vitro.

Conclusions:

  • HBx protein, especially mutant forms, plays a significant role in promoting HBV reactivation.
  • HBV can reactivate from a transcriptionally silenced state.
  • Genotoxic agents can induce HBV reactivation, highlighting potential risks during treatment.