Human immunodeficiency virus type 1 genome activation induced by human T-cell leukemia virus type 1 tax protein is through cooperation of NF-κB and Tat

For productive replication of human immunodeficiency virus type 1 (HIV-1) in host cells, the viral genome-encoded transactivator Tat and several cellular transcription factors are required for efficient viral gene transcription. However, it remains unclear how the viral genome initiates transcription before Tat is transcribed or when Tat is at suboptimal levels. Here, we utilized the human T-cell leukemia type 1 Tax protein as a molecular tool to investigate the mechanism of viral gene transcription that initiates the early phase of infection of HIV-1. Tax alone does not significantly increase the activity of HIV-1 long terminal repeat (LTR) in T lymphocytes, but it markedly enhanced the replication of an infectious HIV-1 provirus with a truncated nef gene. This enhancement is preferentially mediated by the cooperation of Tax and Tat which is dependent on TAR and duplicated kappa B cis elements of the HIV-1 LTR as well as the NF-kappa B activation domain of Tax. Furthermore, phorbol myristate acetate and membrane-targeted HIV-I Nef also enhanced the LTR activity in the presence of Tat in the TAR- and kappa B cis element-dependent manner. These data suggest that activated NF-kappa B can functionally interact with a suboptimal amount of Tat and the HIV-1 LTR for efficient initiation of viral gene transcription.