Interaction of virion protein Vpr of human immunodeficiency virus type 1 with cellular transcription factor Sp1 and trans-activation of viral long terminal repeat.
Acquired immunodeficiency syndrome (AIDS) is a result of replication of the human immunodeficiency virus type 1 (HIV-1) predominantly in CD4+ T lymphocytes and macrophages. However, most of these cells in vivo are immunologically quiescent, a condition restricting HIV-1 replication. Vpr is an HIV-1 virion protein suspected to enhance HIV-1 replication in vivo. We demonstrate in this report that Vpr specifically activates HIV-1 long terminal repeat (LTR)-directed transcription. This effect is most pronounced on a minimal promoter from HIV-1 LTR containing the TATA box and binding motifs for the ubiquitous cellular transcription factor Sp1. Evidence is presented that Vpr interacts with Sp1 when Sp1 is bound to the Sp1 motifs within the HIV-1 LTR Both Vpr-Sp1 interaction and Vpr trans-activation require a central Leu/Ile-rich domain in Vpr. Our findings suggest that Vpr trans-activation through Sp1 is most critical for the immediate early transcription of HIV-1 when other positive regulators, such as NF-kappa B, are limited or inactive, a condition presumably present in vivo. By interacting with Sp1, Vpr also has the potential to influence cellular gene expression and cellular functions. Thus, therapeutic approaches directed toward blocking the Vpr trans-activation function could prove valuable in treating AIDS.
Wang
L
L
Marion Merrell Dow Foundation, Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City 66160-7424, USA.
Mukherjee
S
S
Jia
F
F
Narayan
O
O
Zhao
L J
LJ
D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D016336:Gene Products, vpr / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D016385:TATA Box; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014771:Virion / Q000235:genetics; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D011994:Recombinant Proteins; D016329:Sp1 Transcription Factor; D054325:vpr Gene Products, Human Immunodeficiency Virus