Significance of hepatitis B virus capsid dephosphorylation via polymerase
© 2024. The Author(s)..
BACKGROUND: It is generally believed that hepatitis B virus (HBV) core protein (HBc) dephosphorylation (de-P) is important for viral DNA synthesis and virion secretion. HBV polymerase contains four domains for terminal protein, spacer, reverse transcriptase, and RNase H activities.
METHODS: HBV Polymerase mutants were transfected into HuH-7 cells and assayed for replication and HBc de-P by the Phos-tag gel analysis. Infection assay was performed by using a HepG2-NTCP-AS2 cell line.
RESULTS: Here, we show that a novel phosphatase activity responsible for HBc de-P can be mapped to the C-terminal domain of the polymerase overlapping with the RNase H domain. Surprisingly, while HBc de-P is crucial for viral infectivity, it is essential for neither viral DNA synthesis nor virion secretion. The potential origin, significance, and mechanism of this polymerase-associated phosphatase activity are discussed in the context of an electrostatic homeostasis model. The Phos-tag gel analysis revealed an intriguing pattern of "bipolar distribution" of phosphorylated HBc and a de-P HBc doublet.
CONCLUSIONS: It remains unknown if such a polymerase-associated phosphatase activity can be found in other related biosystems. This polymerase-associated phosphatase activity could be a druggable target in clinical therapy for hepatitis B.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Journal of biomedical science - 31(2024), 1 vom: 01. Apr., Seite 34 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chang, Chih-Hsu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.04.2024 Date Revised 04.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12929-024-01022-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370513428 |
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| 100 | 1 | |a Chang, Chih-Hsu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Significance of hepatitis B virus capsid dephosphorylation via polymerase |
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| 500 | |a Date Completed 03.04.2024 | ||
| 500 | |a Date Revised 04.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: It is generally believed that hepatitis B virus (HBV) core protein (HBc) dephosphorylation (de-P) is important for viral DNA synthesis and virion secretion. HBV polymerase contains four domains for terminal protein, spacer, reverse transcriptase, and RNase H activities | ||
| 520 | |a METHODS: HBV Polymerase mutants were transfected into HuH-7 cells and assayed for replication and HBc de-P by the Phos-tag gel analysis. Infection assay was performed by using a HepG2-NTCP-AS2 cell line | ||
| 520 | |a RESULTS: Here, we show that a novel phosphatase activity responsible for HBc de-P can be mapped to the C-terminal domain of the polymerase overlapping with the RNase H domain. Surprisingly, while HBc de-P is crucial for viral infectivity, it is essential for neither viral DNA synthesis nor virion secretion. The potential origin, significance, and mechanism of this polymerase-associated phosphatase activity are discussed in the context of an electrostatic homeostasis model. The Phos-tag gel analysis revealed an intriguing pattern of "bipolar distribution" of phosphorylated HBc and a de-P HBc doublet | ||
| 520 | |a CONCLUSIONS: It remains unknown if such a polymerase-associated phosphatase activity can be found in other related biosystems. This polymerase-associated phosphatase activity could be a druggable target in clinical therapy for hepatitis B | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Capsids dephosphorylation (de-P) | |
| 650 | 4 | |a HBV core protein (HBc) | |
| 650 | 4 | |a Hepatitis B virus (HBV) | |
| 650 | 4 | |a Phosphatase | |
| 650 | 4 | |a Polymerase (pol) | |
| 650 | 4 | |a RNase H domain | |
| 650 | 7 | |a DNA, Viral |2 NLM | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 650 | 7 | |a Capsid Proteins |2 NLM | |
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