title: HBV maintains electrostatic homeostasis by modulating negative charges from phosphoserine and encapsidated nucleic acids.
abstract: Capsid assembly and stability of hepatitis B virus (HBV) core protein (HBc) particles depend on balanced electrostatic interactions between encapsidated nucleic acids and an arginine-rich domain (ARD) of HBc in the capsid interior. Arginine-deficient ARD mutants preferentially encapsidated spliced viral RNA and shorter DNA, which can be fully or partially rescued by reducing the negative charges from acidic residues or serine phosphorylation of HBc, dose-dependently. Similarly, empty capsids without RNA encapsidation can be generated by ARD hyper-phosphorylation in insect, bacteria, and human hepatocytes. De-phosphorylation of empty capsids by phosphatase induced capsid disassembly. Empty capsids can convert into RNA-containing capsids by increasing HBc serine de-phosphorylation. In an HBV replicon system, we observed a reciprocal relationship between viral and non-viral RNA encapsidation, suggesting both non-viral RNA and serine-phosphorylation could serve as a charge balance buffer in maintaining electrostatic homeostasis. In addition, by comparing the biochemistry assay results between a replicon and a non-replicon system, we observed a correlation between HBc de-phosphorylation and viral replication. Balanced electrostatic interactions may be important to other icosahedral particles in nature.
authors.affiliation: Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.|Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Su
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Ching-Jen
authors.initials: CJ
authors.lastname: Yang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|National Defense Medical Center, Taipei, Taiwan.
authors.forename: Tien-Hua
authors.initials: TH
authors.lastname: Chu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chih-Hsu
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chiayn
authors.initials: C
authors.lastname: Chiang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Fan-Mei
authors.initials: FM
authors.lastname: Tang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chih-Yin
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chiaho
authors.initials: C
authors.lastname: Shih
mesh_terms: D019943:Amino Acid Substitution; D002213:Capsid / Q000378:metabolism*; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D020125:Mutation, Missense; D010768:Phosphoserine / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D055672:Static Electricity
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D010768:Phosphoserine