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 pr omoter binding protein (MBP-1) was subsequently characterized as a cel l regulatory protein with multifunctional activities. In this study, t he role of MBP-1 on human immunodeficiency virus type-1 (HIV-1) transc riptional 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 upstr eam elements of the HIV-1 LTR, including the nuclear factor kappa B (N F-kB) and Sp1 binding sites, did not affect the MBP-1 mediated suppres sion of HIV-1 LTR. The core promoter of the HIV-1 appeared to be the p rimary sequence involved in MBP-1 mediated inhibition. In the presence of HIV-1 TAR sequence and Tat protein, MBP-1 did not inhibit the vira l promoter activity. In addition, cotransfection experiments with HIV- 1 LTR and deletion mutants of MBP-1 suggested that the carboxyl termin al half of MBP-1 suppresses the HIV-1 promoter activity. Exogenous exp ression of MBP-1 showed suppression of HIV-1 replication in acutely in fected cells and in cells cotransfected with a molecular clone of HIV- 1. These results suggest that exogenous expression of MBP-1 plays an i mportant role in the regulation of HIV-1 replication in infected cells . (C) 1997 Wiley-Liss, Inc.