biostudies-literatureChu JYKHHS | NIH | Office of Extramural Research, National Institutes of HealthNIDDK NIH HHSNIAID NIH HHSe2201927119https://www.ebi.ac.uk/biostudies/studies/S-EPMC9335259biostudies-literatureUnknown119(30)Hepatitis B virus (HBV) DNA replication takes place inside the viral core particle and is dependent on autophagy. Here we show that HBV core particles are associated with autophagosomes and phagophores in cells that productively replicate HBV. These autophagic membrane-associated core particles contain almost entirely the hypophosphorylated core protein and are DNA replication competent. As the hyperphosphorylated core protein can be localized to phagophores and the dephosphorylation of the core protein is associated with the packaging of viral pregenomic RNA (pgRNA), these results are in support of the model that phagophores can serve as the sites for the packaging of pgRNA. In contrast, in cells that replicate HBV, the precore protein derivatives, which are related to the core protein, aProceedings of the National Academy of Sciences of the United States of AmericaAutophagic membranes participate in hepatitis B virus nucleocapsid assembly, precore and core protein trafficking, and viral release.PMC9335259R21 AI139954R01 DK094652R01 DK101773AI145813R01 AI145813R01 AI148304R37 AI129540AI148305AI129540R01 AI129540Ishida YTsai KNSaito TOu JJChu JYKPantuso JChuang YCfalseAutophagic membranes participate in hepatitis B virus nucleocapsid assembly, precore and core protein trafficking, and viral release.Hepatitis B virus (HBV) DNA replication takes place inside the viral core particle and is dependent on autophagy. Here we show that HBV core particles are associated with autophagosomes and phagophores in cells that productively replicate HBV. These autophagic membrane-associated core particles contain almost entirely the hypophosphorylated core protein and are DNA replication competent. As the hyperphosphorylated core protein can be localized to phagophores and the dephosphorylation of the core protein is associated with the packaging of viral pregenomic RNA (pgRNA), these results are in support of the model that phagophores can serve as the sites for the packaging of pgRNA. In contrast, in cells that replicate HBV, the precore protein derivatives, which are related to the core protein, a2022-01-01T00:00:00Z2022 Jul2025-04-04T20:07:11.424Z2025-04-04T20:07:11.424ZS-EPMC93352593585842610.1073/pnas.2201927119