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- Title
Significance of hepatitis B virus capsid dephosphorylation via polymerase.
- Authors
Chang, Chih-Hsu; Shih, Chiaho
- Abstract
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.
- Subjects
HEPATITIS B virus; RIBONUCLEASE H; DEPHOSPHORYLATION; VIRAL DNA; DNA synthesis
- Publication
Journal of Biomedical Science, 2024, Vol 31, Issue 1, p1
- ISSN
1021-7770
- Publication type
Article
- DOI
10.1186/s12929-024-01022-9