Control of hutnan imtnunodeficiency virus gene expression by the RNA-binding proteins tat and rev

Abstract Replication of the human immunodeficiency virus (HIV) is controlled by two viral proteins, the trans-activator protein (tat) and the regulator of virion expression (rev). These regulatory proteins play complementary roles in the HIV life cycle: tat stimulates transcription from the viral long-terminal repeat (LTR), whereas rev is required for the efficient cytoplasmic expression of the mRNAs encoding the structural proteins of the virus. This system of dual regulation is illustrated in Figure 1. In permissive cells, transcription of the integrated proviral genome is initiated by host cell transcription factors (1-3). Initially, a low level of small, multiply spliced mRNAs encoding tat and rev are produced (4). tat synthesized during the primary round of transcription establishes a ‘positive feedback loop’ which boosts tat and rev mRNA production 200-1000-fold (5-7). Once a critical rev threshold is surpassed, HIV gene expression switches away from the production of the mRNAs for the regulatory proteins towards the production of the unspliced or partially spliced mRNAs encoding the virion proteins (8-10).