A Novel Chromosome Region Maintenance 1-independent Nuclear Export Signal of the Large Form of Hepatitis Delta Antigen That Is Required for the Viral Assembly
Journal
Journal of Biological Chemistry
Journal Volume
276
Journal Issue
11
Pages
8142-8148
Date Issued
2001
Author(s)
Abstract
Hepatitis 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
Other Subjects
Amino 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 Assembly
Type
journal article