TY - JOUR
T1 - Heat-shock protein 70 exerts opposing effects on Vpr-dependent and Vpr-independent HIV-1 replication in macrophages
AU - Iordanskiy, Sergey
AU - Zhao, Yuqi
AU - DiMarzio, Paola
AU - Agostini, Isabelle
AU - Dubrovsky, Larisa
AU - Bukrinsky, Michael
PY - 2004/9/15
Y1 - 2004/9/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2004-01-0081
DO - 10.1182/blood-2004-01-0081
M3 - Article
C2 - 15166037
AN - SCOPUS:4444306891
SN - 0006-4971
VL - 104
SP - 1867
EP - 1872
JO - Blood
JF - Blood
IS - 6
ER -