Heat shock protein 70 protects cells from cell cycle arrest and apoptosis induced by human immunodeficiency virus type 1 viral protein R.
Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) is an accessory protein that plays an important role in viral pathogenesis. This pathogenic activity of Vpr is related in part to its capacity to induce cell cycle G2 arrest and apoptosis of target T cells. A screening for multicopy suppressors of these Vpr activities in fission yeast identified heat shock protein 70 (Hsp70) as a suppressor of Vpr-induced cell cycle arrest. Hsp70 is a member of a family of molecular chaperones involved in innate immunity and protection from environmental stress. In this report, we demonstrate that HIV-1 infection induces Hsp70 in target cells. Overexpression of Hsp70 reduced the Vpr-dependent G2 arrest and apoptosis and also reduced replication of the Vpr-positive, but not Vpr-deficient, HIV-1. Suppression of Hsp70 expression by RNA interference (RNAi) resulted in increased apoptosis of cells infected with a Vpr-positive, but not Vpr-defective, HIV-1. Replication of the Vpr-positive HIV-1 was also increased when Hsp70 expression was diminished. Vpr and Hsp70 coimmunoprecipitated from HIV-infected cells. Together, these results identify Hsp70 as a novel anti-HIV innate immunity factor that targets HIV-1 Vpr.
The George Washington University, Ross Hall Rm. 734, 2300 Eye St. N.W., Washington, DC 20037, USA.
Sergey
S
Iordanskiy
Yuqi
Y
Zhao
Larisa
L
Dubrovsky
Tatiana
T
Iordanskaya
Mongzhong
M
Chen
Dong
D
Liang
Michael
M
Bukrinsky
D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D004247:DNA / Q000235:genetics; D016336:Gene Products, vpr / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D034622:RNA Interference; 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; D004247:DNA