Anti-vpr activities of heat shock protein 27.
HIV-1 Vpr plays a pivotal role in viral pathogenesis and is preferentially targeted by the host immune system. In this report, we demonstrate that a small heat shock protein, HSP27, exhibits Vpr-specific antiviral activity, as its expression is specifically responsive to vpr gene expression and increased levels of HSP27 inhibit Vpr-induced cell cycle G2 arrest and cell killing. We further show that overexpression of HSP27 reduces viral replication in T-lymphocytes in a Vpr-dependent manner. Mechanistically, Vpr triggers HSP27 expression through heat shock factor (HSF) 1, but inhibits prolonged expression of HSP27 under heat-shock conditions. Together, these data suggest a potential dynamic and antagonistic interaction between HIV-1 Vpr and a host cell HSP27, suggesting that HSP27 may contribute to cellular intrinsic immunity against HIV infection.
Liang
Dong
D
Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Benko
Zsigmond
Z
Agbottah
Emmanuel
E
Bukrinsky
Michael
M
Zhao
Richard Y
RY
D017209:Apoptosis; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D016195:G2 Phase; D015870:Gene Expression; D016336:Gene Products, vpr / Q000037:antagonists & inhibitors*; D015658:HIV Infections; D015497:HIV-1 / Q000502:physiology; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response; D006801:Humans; D013601:T-Lymphocytes / Q000821:virology; D014157:Transcription Factors / Q000378:metabolism; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
D004268:DNA-Binding Proteins; D016336:Gene Products, vpr; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D014157:Transcription Factors; D054325:vpr Gene Products, Human Immunodeficiency Virus