title: Hepatitis delta virus ribonucleoproteins shuttle between the nucleus and the cytoplasm.
abstract: Hepatitis delta virus (HDV) infection of individuals infected with hepatitis B virus (HBV) is associated with more severe liver damage and an increased risk of fulminant disease. HDV is a single-stranded RNA virus that encodes a single protein, the delta antigen, which is expressed in two forms, small (S-HDAg) and large (L-HDAg). Here we show that although HDV ribonucleoproteins are mainly detected in the nucleus, they are also present in the cytoplasm of cells infected with HDV or transfected with HDV cDNA. Making use of an heterokaryon assay, we demonstrate that HDV ribonucleoproteins shuttle continuously between the nucleus and the cytoplasm. In the absence of HDV RNA, both forms of the delta antigen are retained in the nucleus, whereas in the absence of the delta antigen, HDV RNA is predominantly detected in the cytoplasm. Coexpression of HDV RNA and S-HDAg (which binds to the viral RNA and contains a nuclear localization signal) results in nuclear accumulation of the viral RNA. This suggests that HDV RNA mediates export of viral particles to the cytoplasm whereas the delta antigen triggers their reimport into the nucleus.
authors.affiliation: Institute of Histology and Embryology, Faculty of Medicine, University of Lisbon, Portugal.
authors.forename: João P
authors.initials: JP
authors.lastname: Tavanez
authors.forename: Celso
authors.initials: C
authors.lastname: Cunha
authors.forename: Maria C A
authors.initials: MC
authors.lastname: Silva
authors.forename: Ezio
authors.initials: E
authors.lastname: David
authors.forename: João
authors.initials: J
authors.lastname: Monjardino
authors.forename: Maria
authors.initials: M
authors.lastname: Carmo-Fonseca
mesh_terms: D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus; D000818:Animals; D001693:Biological Transport, Active; D002460:Cell Line; D002467:Cell Nucleus / Q000821:virology; D003593:Cytoplasm / Q000821:virology; D016679:Genome, Viral; D018963:Hepatitis Antigens / Q000378:metabolism; D006509:Hepatitis B / Q000150:complications; D003699:Hepatitis D / Q000150:complications / Q000821:virology*; D003698:Hepatitis Delta Virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D035923:Hepatitis delta Antigens; D006801:Humans; D008099:Liver / Q000821:virology; D051379:Mice; D008954:Models, Biological; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D014162:Transfection; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D018963:Hepatitis Antigens; D035923:Hepatitis delta Antigens; D012367:RNA, Viral; D012261:Ribonucleoproteins; D014764:Viral Proteins; C442244:hepatitis delta virus large antigen