Poster abstracts

Poster number 23 submitted by Uri Mbonye

Reactivation of Processive HIV proviral transcription by T cell receptor signaling

Uri Mbonye (Molecular Biology and Microbiology, Case Western Reserve University), Young Kyeung Kim (Molecular Biology and Microbiology, Case Western Reserve University), Joseph Hokello (Molecular Biology and Microbiology, Case Western Reserve University), Jonathan Karn (Molecular Biology and Microbiology, Case Western Reserve University)

Abstract:
A strict regimen of highly active antiretroviral therapy (HAART) administered to HIV infected individuals is unable to eliminate latent HIV proviruses that are stably integrated in the genome of a very small population of long-lived memory CD4+ T lymphocytes. When HAART is interrupted, T cell receptor stimulation during foreign antigen presentation induces the reactivation of latent HIV expression. In a latent HIV Jurkat T cell model, initiation of T cell receptor (TCR) signaling stimulates rapid transcription elongation of the HIV provirus. TCR-activated processive proviral transcription is mediated by the MAPK/ERK pathway which induces the release of the HIV Tat elongation co-factor P-TEFb from its inactive nuclear regulatory 7SK snRNP complex. Defining the biochemical mechanisms for the release of P-TEFb from 7SK snRNP and its recruitment to the HIV gene could prove useful in developing therapies that specifically target the reactivation of latent HIV expression.

Keywords: HIV latency; Transcription elongation; P-TEFb, 7SK snRNP; 7SK snRNA