NOVEL MECHANISM AND HOST COFACTORS FOR REGULATION OF HIV‐1 TRANSCRIPTION

Abstract

Recruited by HIV Tat and TAR to the viral LTR, human transcription elongation factor P-TEFb phosphorylates RNA polymerase II and negative elongation factors to stimulate HIV transcription and replication. Since 1997, this discovery has provided the basic framework for our understanding of Tat function in the HIV life cycle and a paradigm for studying eukaryotic elongation control in general. Although P-TEFb remains the widely accepted Tat partner till this day, accumulating evidence suggests that Tat-transactivation involves more than the interaction between Tat and P-TEFb. In an effort to identify additional cellular factors that associate with Tat and P-TEFb, we have identified transcription elongation factor ELL2 and transcription factors AFF4, ENL and AF9 as new Tat partners. These factors join Tat and P-TEFb to form a multi-subunit complex called BFEC. Data will be presented to demonstrate how BFEC interacts with a chromatin template, stimulates basal and Tat-activated HIV transcription, and is stabilized in response to signals that activate HIV gene expression. The identification and characterization of BFEC will enable a better understanding of the mechanisms controlling HIV and cellular transcriptional elongation and may reveal novel strategies to reactivate latent HIV for eradication.