title: Expression of viral polymerase and phosphorylation of core protein determine core and capsid localization of the human hepatitis B virus.
abstract: Biopsies from patients show that hepadnaviral core proteins and capsids - collectively called core - are found in the nucleus and cytoplasm of infected hepatocytes. In the majority of studies, cytoplasmic core localization is related to low viraemia while nuclear core localization is associated with high viral loads. In order to better understand the molecular interactions leading to core localization, we analysed transfected hepatoma cells using immune fluorescence microscopy. We observed that expression of core protein in the absence of other viral proteins led to nuclear localization of core protein and capsids, while expression of core in the context of the other viral proteins resulted in a predominantly cytoplasmic localization. Analysis of which viral partner was responsible for cytoplasmic retention indicated that the HBx, surface proteins and HBeAg had no impact but that the viral polymerase was the major determinant. Further analysis revealed that ϵ, an RNA structure to which the viral polymerase binds, was essential for cytoplasmic retention. Furthermore, we showed that core protein phosphorylation at Ser 164 was essential for the cytoplasmic core localization phenotype, which is likely to explain differences observed between individual cells.
authors.affiliation: Hepatitis Virus Diversity Research Programme, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa.|CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.|Univ. de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Deroubaix
authors.affiliation: CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.|Univ. de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Osseman
authors.affiliation: CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.|Univ. de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Cassany
authors.affiliation: CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.|Univ. de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bégu
authors.affiliation: CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.|Univ. de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ragues
authors.affiliation: CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.|Univ. de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.
authors.forename: Somar
authors.initials: S
authors.lastname: Kassab
authors.affiliation: CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.|Univ. de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.|Université Montpellier 1, CPBS, UMR 5236 CNRS, Montpellier, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lainé
authors.affiliation: Univ. de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.|CHU de Bordeaux, Bordeaux, France.|CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Kann
mesh_terms: D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D056945:Hep G2 Cells; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000235:genetics*; D014162:Transfection / Q000379:methods; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D006513:Hepatitis B e Antigens; D014758:Viral Core Proteins; D004259:DNA-Directed DNA Polymerase