{Reference Type}: Journal Article
{Title}: Significance of hepatitis B virus capsid dephosphorylation via polymerase.
{Author}: Chang CH;Shih C;
{Journal}: J Biomed Sci
{Volume}: 31
{Issue}: 1
{Year}: 2024 Apr 1
{Factor}: 12.771
{DOI}: 10.1186/s12929-024-01022-9
{Abstract}: <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.