Lee C.-H.SHIN CHANGWu C.H.H.MING-FU CHANG2019-11-112019-11-112001https://www.scopus.com/inward/record.uri?eid=2-s2.0-0035896539&doi=10.1074%2fjbc.M004477200&partnerID=40&md5=e1f6994cb8f1397e12a238d19c386d2bhttps://scholars.lib.ntu.edu.tw/handle/123456789/431074Hepatitis delta virus (HDV) is a satellite virus of hepatitis B virus, as it requires hepatitis B virus for virion production and transmission. We have previously demonstrated that sequences within the C-terminal 19-amino acid domain flanking the isoprenylation motif of the large hepatitis delta antigen (HDAg-L) are important for virion assembly. In this study, site-directed mutagenesis and immunofluorescence staining demonstrated that in the absence of hepatitis B virus surface antigen (HBsAg), the wild-type HDAg-L was localized in the nuclei of transfected COS7 cells. Nevertheless, in the presence of HBsAg, the HDAg-L became both nuclei- and cytoplasm-distributed in about half of the cells. An HDAg-L mutant with a substitution of Pro-205 to alanine could neither form HDV-like particles nor shift the subcellular localization in the presence of HBsAg. In addition, nuclear trafficking of HDAg-L in heterokaryons indicated that HDAg-L is a nucleocytoplasmic shuttling protein. A proline-rich HDAg peptide spanning amino acid residues 198 to 210, designated NES(HDAg-L), can function as a nuclear export signal (NES) in Xenopus oocytes. Pro-205 is critical for the NES function. Furthermore, assembly of HDV is insensitive to leptomycin B, indicating that the NES(HDAg-L) directs nuclear export of HDAg-L to the cytoplasm via a chromosome region maintenance 1-independent pathway.[SDGs]SDG3Amino acids; Antigens; Chromosomes; Cytology; Fluorescence; Immunology; Mutagenesis; Immunofluorescence; Virion transmission; Viruses; hepatitis B surface antigen; hepatitis delta antigen; hepatitis antigen; hepatitis B surface antigen; hepatitis delta antigen; hepatitis delta virus large antigen; leptomycin B; unsaturated fatty acid; animal cell; article; cell strain COS7; Hepatitis delta virus; nonhuman; priority journal; protein localization; protein protein interaction; signal transduction; virus assembly; virus cell interaction; active transport; animal; cell line; chromosome; cytoplasm; drug effect; Hepatitis delta virus; human; metabolism; mouse; physiology; Animalia; Hepatitis B virus; Hepatitis delta virus; Nes; Satellite Viruses; delta virus; Active Transport, Cell Nucleus; Animals; Cell Line; Chromosomes; Cytoplasm; Fatty Acids, Unsaturated; Hepatitis Antigens; Hepatitis B Surface Antigens; Hepatitis delta Antigens; Hepatitis Delta Virus; Humans; Mice; Virus Assemblyjournal article10.1074/jbc.M0044772002-s2.0-0035896539