RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/36990397http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36990397http://www.w3.org/2000/01/rdf-schema#comment"Human parvovirus B19 (B19V) is a major human pathogen causing a variety of diseases, characterized by a selective tropism to human progenitor cells in bone marrow. In similar fashion to all Parvoviridae members, the B19V ssDNA genome is replicated within the nucleus of infected cells through a process which involves both cellular and viral proteins. Among the latter, a crucial role is played by non-structural protein (NS)1, a multifunctional protein involved in genome replication and transcription, as well as modulation of host gene expression and function. Despite the localization of NS1 within the host cell nucleus during infection, little is known regarding the mechanism of its nuclear transport pathway. In this study we undertake structural, biophysical, and cellular approaches to characterize this process. Quantitative confocal laser scanning microscopy (CLSM), gel mobility shift, fluorescence polarization and crystallographic analysis identified a short sequence of amino acids (GACHAKKPRIT-182) as the classical nuclear localization signal (cNLS) responsible for nuclear import, mediated in an energy and importin (IMP) α/β-dependent fashion. Structure-guided mutagenesis of key residue K177 strongly impaired IMPα binding, nuclear import, and viral gene expression in a minigenome system. Further, treatment with ivermectin, an antiparasitic drug interfering with the IMPα/β dependent nuclear import pathway, inhibited NS1 nuclear accumulation and viral replication in infected UT7/Epo-S1 cells. Thus, NS1 nuclear transport is a potential target of therapeutic intervention against B19V induced disease."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.org/dc/terms/identifier"doi:10.1016/j.antiviral.2023.105588"xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/author"Gallinella G."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/author"Alvisi G."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/author"Akbari N."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/author"Cross E.M."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/author"Forwood J."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/author"Pavan S."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/author"Petersen G.F."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/author"Hoad M."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/author"Bua G."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/author"Ariawan D."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/author"Manaresi E."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/name"Antiviral Res"xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/pages"105588"xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/title"Importin alpha/beta-dependent nuclear transport of human parvovirus B19 nonstructural protein 1 is essential for viral replication."xsd:string
http://purl.uniprot.org/citations/36990397http://purl.uniprot.org/core/volume"213"xsd:string
http://purl.uniprot.org/citations/36990397http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36990397
http://purl.uniprot.org/citations/36990397http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/36990397
http://purl.uniprot.org/uniprot/#_P52293-mappedCitation-36990397http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36990397
http://purl.uniprot.org/uniprot/#_Q9PZT1-mappedCitation-36990397http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36990397
http://purl.uniprot.org/uniprot/Q9PZT1http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/36990397
http://purl.uniprot.org/uniprot/P52293http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/36990397