Inhibition of human immunodeficiency virus type 1 replication by a cellular transcriptional factor MBP-1.
A cellular transcriptional factor initially identified as the c-myc promoter binding protein (MBP-1) was subsequently characterized as a cell regulatory protein with multifunctional activities. In this study, the role of MBP-1 on human immunodeficiency virus type-1 (HIV-1) transcriptional activity was investigated. MBP-1 showed inhibition of HIV-1 long terminal repeat (LTR)-directed chloramphenicol acetyl transferase (CAT) activity in a transient cotransfection assay. Deletion of upstream elements of the HIV-1 LTR, including the nuclear factor kappa B (NF-kappa B) and Sp1 binding sites, did not affect the MBP-1 mediated suppression of HIV-1 LTR. The core promoter of the HIV-1 appeared to be the primary sequence involved in MBP-1 mediated inhibition. In the presence of HIV-1 TAR sequence and Tat protein, MBP-1 did not inhibit the viral promoter activity. In addition, cotransfection experiments with HIV-1 LTR and deletion mutants of MBP-1 suggested that the carboxyl terminal half of MBP-1 suppresses the HIV-1 promoter activity. Exogenous expression of MBP-1 showed suppression of HIV-1 replication in acutely infected cells and in cells cotransfected with a molecular clone of HIV-1. These results suggest that exogenous expression of MBP-1 plays an important role in the regulation of HIV-1 replication in infected cells.
Ray
R B
RB
Department of Internal Medicine, St. Louis University, Missouri 63110-0250, USA. Rayrb@sluvca.slu.edu
Srinivas
R V
RV
D004268:DNA-Binding Proteins / Q000502:physiology*; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D014157:Transcription Factors; D014779:Virus Replication / Q000502:physiology*
D004268:DNA-Binding Proteins; C063232:HIVEP1 protein, human; D014157:Transcription Factors