title: Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex.
abstract: Replication of human immunodeficiency virus type 1 (HIV-1) in non-dividing cells depends critically on import of the viral preintegration complex into the nucleus. Recent evidence suggests that viral protein R (Vpr) plays a key regulatory role in this process by binding to karyopherin alpha, a cellular receptor for nuclear localization signals, and increasing its affinity for the nuclear localization signals. An in vitro binding assay was used to investigate the role of Vpr in docking of the HIV-1 preintegration complex (PIC) to the nuclear pore complex. Mutant HIV-1 PICs that lack Vpr were impaired in the ability to dock to isolated nuclei and recombinant nucleoporins. Although Vpr by itself associated with nucleoporins, the docking of Vpr+ PICs was dependent on karyopherin beta and was blocked by antibodies to beta. Vpr stabilized docking by preventing nucleoporin-stimulated dissociation of the import complex. These results suggest a biochemical mechanism for Vpr function in transport of the HIV-1 genome across the nuclear pore complex.
authors.affiliation: The Picower Institute for Medical Research, Manhasset, New York 11030, USA.
authors.forename: S
authors.initials: S
authors.lastname: Popov
authors.forename: M
authors.initials: M
authors.lastname: Rexach
authors.forename: L
authors.initials: L
authors.lastname: Ratner
authors.forename: G
authors.initials: G
authors.lastname: Blobel
authors.forename: M
authors.initials: M
authors.lastname: Bukrinsky
mesh_terms: D002460:Cell Line; D016336:Gene Products, vpr / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009685:Nuclear Envelope / Q000821:virology*; D019913:Nuclear Localization Signals / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D016662:Virus Integration; D028961:beta Karyopherins; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D016336:Gene Products, vpr; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D028961:beta Karyopherins; D054325:vpr Gene Products, Human Immunodeficiency Virus