REGULATION OF HUMAN RETROVIRAL LATENCY BY THE NF-KAPPA-B I-KAPPA-B FAMILY - INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION BY I-KAPPA-B THROUGH A REV-DEPENDENT MECHANISM/

The cellular transcription factor NF-kappa B stimulates human immunode ficiency virus type 1 (HIV-1) transcriptional initiation, but its role in the retroviral life cycle has not been fully defined. In this repo rt, we show that I kappa B alpha acts as a cellular inhibitor of human retroviral replication through a discrete mechanism, independent of i ts effect on HIV transcription, I kappa B alpha inhibited HIV replicat ion and gp160 expression by negatively regulating Rev function, most l ikely acting through a cellular factor involved in Rev transactivation , A similar effect was observed with human T leukemia virus I, in whic h I kappa B alpha inhibited Rex function, In contrast, no effect was, observed on the replication of a DNA virus, adenovirus type 5, The NF- kappa B/I kappa B regulatory pathway therefore modulates human retrovi ral replication by regulating a program of cellular gene expression re quired for several steps in the viral life cycle, including not only v iral transcription but also RNA export, This interaction between cellu lar and viral gene products suggests that NF-kappa B plays a broader r ole in the regulation of human retroviral replication, providing a pre viously unrecognized link between two important regulators of HIV gene expression and common NF-kappa B-dependent programs of gene expressio n used by human retroviruses.