Heat-shock protein 70 exerts opposing effects on Vpr-dependent and Vpr-independent HIV-1 replication in macrophages.
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.
Iordanskiy
Sergey
S
The George Washington University, Washington, DC 20037, USA.
Zhao
Yuqi
Y
DiMarzio
Paola
P
Agostini
Isabelle
I
Dubrovsky
Larisa
L
Bukrinsky
Michael
M
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
D016336:Gene Products, vpr; D018840:HSP70 Heat-Shock Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus