Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids.
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 o...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-07-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008669 |
| _version_ | 1829502671250259968 |
|---|---|
| author | Zhanying Hu Haiqun Ban Haiyan Zheng Mingliang Liu Jinhong Chang Ju-Tao Guo |
| author_facet | Zhanying Hu Haiqun Ban Haiyan Zheng Mingliang Liu Jinhong Chang Ju-Tao Guo |
| author_sort | Zhanying Hu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T09:42:56Z |
| format | Article |
| id | doaj.art-d61fe61bb14b4832a7afb06f44f38204 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T09:42:56Z |
| publishDate | 2020-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-d61fe61bb14b4832a7afb06f44f382042022-12-21T22:36:14ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-07-01167e100866910.1371/journal.ppat.1008669Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids.Zhanying HuHaiqun BanHaiyan ZhengMingliang LiuJinhong ChangJu-Tao GuoHepatitis 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.https://doi.org/10.1371/journal.ppat.1008669 |
| spellingShingle | Zhanying Hu Haiqun Ban Haiyan Zheng Mingliang Liu Jinhong Chang Ju-Tao Guo Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids. PLoS Pathogens |
| title | Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids. |
| title_full | Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids. |
| title_fullStr | Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids. |
| title_full_unstemmed | Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids. |
| title_short | Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids. |
| title_sort | protein phosphatase 1 catalyzes hbv core protein dephosphorylation and is co packaged with viral pregenomic rna into nucleocapsids |
| url | https://doi.org/10.1371/journal.ppat.1008669 |
| work_keys_str_mv | AT zhanyinghu proteinphosphatase1catalyzeshbvcoreproteindephosphorylationandiscopackagedwithviralpregenomicrnaintonucleocapsids AT haiqunban proteinphosphatase1catalyzeshbvcoreproteindephosphorylationandiscopackagedwithviralpregenomicrnaintonucleocapsids AT haiyanzheng proteinphosphatase1catalyzeshbvcoreproteindephosphorylationandiscopackagedwithviralpregenomicrnaintonucleocapsids AT mingliangliu proteinphosphatase1catalyzeshbvcoreproteindephosphorylationandiscopackagedwithviralpregenomicrnaintonucleocapsids AT jinhongchang proteinphosphatase1catalyzeshbvcoreproteindephosphorylationandiscopackagedwithviralpregenomicrnaintonucleocapsids AT jutaoguo proteinphosphatase1catalyzeshbvcoreproteindephosphorylationandiscopackagedwithviralpregenomicrnaintonucleocapsids |