The Tat/P-TEFb Protein-Protein Interaction Determining Transcriptional Activation of HIV

Human immunodeficiency virus type (HIV) transcription is crucial for its life cycle and is primarily involved in the maintenance of viral latency. HIV transcription is regulated by both viral and cellular transcription factors. Numerous epigenetic factors, as well as transcriptional suppressor proteins, play major roles in the maintenance of transcriptional silencing of viral gene expression from the proviral DNA. Once inducible transcription factors such as nuclear factor ΚB are activated through extracellular signaling, viral latency is terminated and transcription from the silenced proviral DNA is initiated. Transcriptional induction by cellular factors is immediately followed by high gene expression via the function of the virus-encoded transcriptional activator Tat. Interestingly, unlike other known transcriptional activators, Tat primarily activates transcriptional elongation, rather than initiation, by interacting with and activating cellular positive transcriptional elongation factor b (P-TEFb). In this review, we describe how HIV transcription is negatively and positively regulated through its life cycle and the molecular mechanism underlying how Tat activates viral transcription. We propose a novel strategy against viral replication in which regulated transcriptional processes play important roles in determining the extent of viral replication. The structural details of how Tat interacts with P-TEFb are described, which may be useful for the development of effective and specific anti-HIV therapies.