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Autophagic membranes participate in hepatitis B virus nucleocapsid assembly, precore and core protein trafficking,

Ja Yeon Kim Chu1, Yu-Chen Chuang1, Kuen-Nan Tsai1

  • 1Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033.

Proceedings of the National Academy of Sciences of the United States of America
|July 20, 2022
PubMed

Insights

Hepatitis B virus (HBV) utilizes autophagy for replication. Autophagic membranes are involved in HBV core particle assembly, protein trafficking, and particle release, highlighting a crucial role for autophagy in the HBV life cycle.

Area of Science:

  • Cell Biology
  • Virology
  • Molecular Biology

Background:

  • Hepatitis B virus (HBV) replication is intrinsically linked to cellular autophagy.
  • Understanding the precise mechanisms of HBV assembly and trafficking within host cells is crucial for developing antiviral strategies.

Purpose of the Study:

  • To elucidate the role of autophagic membranes in Hepatitis B virus (HBV) replication.
  • To investigate the differential involvement of autophagic pathways in the trafficking of HBV core and precore proteins.
  • To explore the impact of autophagy on HBV nucleocapsid assembly and particle release.

Main Methods:

  • Immunofluorescence microscopy to visualize HBV core particles and autophagosomes/phagophores.
  • Analysis of core protein phosphorylation status in association with autophagic membranes.
  • Investigation of precore protein localization and its dependence on signal peptides.
  • Assessment of HBV particle release upon manipulation of autophagy regulators like Rab11.

Main Results:

  • HBV core particles associate with autophagosomes and phagophores, containing hypophosphorylated core protein competent for DNA replication.
  • Phagophores are implicated as sites for packaging of viral pregenomic RNA (pgRNA) via core protein dephosphorylation.
  • Precore protein derivatives associate with autophagosomes independently of their signal peptide, while core protein alone associates with phagophores.
  • HBV induces autophagosome-multivesicular body fusion, and Rab11 silencing reduces mature HBV particle release.

Conclusions:

  • Autophagic membranes play a multifaceted role in the HBV life cycle, including nucleocapsid assembly and protein trafficking.
  • Differential association of HBV core and precore proteins with autophagic compartments suggests distinct regulatory mechanisms.
  • Autophagy modulation impacts HBV particle egress, indicating its importance in viral dissemination.
Keywords:
HBV protein traffickingautophagosomesautophagyhepatitis B virusphagophores

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