Journal article
Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids
PLoS pathogens, v 16(7), pp e1008669-e1008669
01 Jul 2020
PMID: 32702076
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hepatitis B virus (HBV) replicates its genomic DNA via viral DNA polymerase self-primed reverse transcription of a RNA pre-genome in the nucleocapsid assembled by 120 core protein (Cp) dimers. The arginine-rich carboxyl-terminal domain (CTD) of Cp plays an important role in the selective packaging of viral DNA polymerase-pregenomic (pg) RNA complex into nucleocapsid. Previous studies suggested that the CTD is initially phosphorylated at multiple sites to facilitate viral RNA packaging and subsequently dephosphorylated in association with viral DNA synthesis and secretion of DNA-containing virions. However, our recent studies suggested that Cp is hyper-phosphorylated as free dimers and its dephosphorylation is associated with pgRNA encapsidation. Herein, we provide further genetic and biochemical evidence supporting that extensive Cp dephosphorylation does take place during the assembly of pgRNA-containing nucleocapsids, but not empty capsids. Moreover, we found that cellular protein phosphatase 1 (PP1) is required for Cp dephosphorylation and pgRNA packaging. Interestingly, the PP1 catalytic subunits α and β were packaged into pgRNA-containing nucleocapsids, but not empty capsids, and treatment of HBV replicating cells with core protein allosteric modulators (CpAMs) promoted empty capsid assembly and abrogated the encapsidation of PP1 α and β. Our study thus identified PP1 as a host cellular factor that is co-packaged into HBV nucleocapsids, and plays an essential role in selective packaging of the viral DNA-polymerase-pgRNA complex through catalyzing Cp dephosphorylation.
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Details
- Title
- Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids
- Creators
- Zhanying Hu - Baruch S. Blumberg InstituteHaiqun Ban - Baruch S. Blumberg InstituteHaiyan Zheng - Rutgers, The State University of New JerseyMingliang Liu - Chinese Academy of Medical Sciences & Peking Union Medical CollegeJinhong Chang - Baruch S. Blumberg InstituteJu-Tao Guo - Baruch S. Blumberg Institute
- Publication Details
- PLoS pathogens, v 16(7), pp e1008669-e1008669
- Publisher
- Public LIbrary of Science (PLOS)
- Grant note
- R01 AI113267 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000596619500006
- Scopus ID
- 2-s2.0-85089163715
- Other Identifier
- 991020547439004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Microbiology
- Parasitology
- Virology