title: Heat-shock protein 70 exerts opposing effects on Vpr-dependent and Vpr-independent HIV-1 replication in macrophages.
abstract: HIV-1 viral protein R (Vpr) shuttles between the nucleus and the cytoplasm and is believed to contribute to the process of nuclear translocation of the viral preintegration complex, thus facilitating HIV-1 replication in macrophages. In this report, we demonstrate that Hsp70, a heat-shock protein contributing to cellular stress responses, inhibits nuclear translocation of HIV-1 Vpr. In macrophages, Hsp70 is induced shortly after HIV-1 infection. Recombinant Hsp70 or a mild heat shock diminished replication of the wild-type HIV-1, suggesting that Hsp70 might function as an innate antiviral factor. Surprisingly, Hsp70 stimulated nuclear import and replication in macrophages of the Vpr-deficient HIV-1 construct. This finding suggests that Hsp70 and Vpr may function in a similar manner when expressed separately, but they neutralize each other's activity when present together. Consistent with this interpretation, Hsp70 coprecipitated with Vpr from HIV-1-infected cells.
authors.affiliation: The George Washington University, Washington, DC 20037, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Iordanskiy
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Paola
authors.initials: P
authors.lastname: DiMarzio
authors.forename: Isabelle
authors.initials: I
authors.lastname: Agostini
authors.forename: Larisa
authors.initials: L
authors.lastname: Dubrovsky
authors.forename: Michael
authors.initials: M
authors.lastname: Bukrinsky
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism; D016336:Gene Products, vpr / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000821:virology*; D011233:Precipitin Tests; D011485:Protein Binding; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D016336:Gene Products, vpr; D018840:HSP70 Heat-Shock Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus