HIV Research Today is a free monthly online journal that collates and summarizes the latest research about HIV, including details on human immunodeficiency virus, testing, treatment, prevention, vaccines, aids.

Cooperativity between Rad51 and C/EBP family transcription factors modulates basal and Tat-induced activation of the HIV-1 LTR in astrocytes.

Chipitsyna G, Sawaya BE, Khalili K, Amini S

Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19122, USA.

Transcription of the HIV-1 genome is a complex event that requires functional and physical communication of cellular proteins that recognize the LTR sequence with viral proteins, most notably, Tat. Moreover, studies have revealed the ability of Tat to induce transcription of a variety of cellular genes whose products can affect the status of cells, thus contributing to the pathogenesis of AIDS. Recently, we demonstrated that expression of Tat in astrocytes and other neural cells leads to upregulation of Rad51, a major component of DNA repair via homologous recombination. The unscheduled upregulation of Rad51, in turn, has an impact upon the extent of chromosomal abnormalities that are seen in Tat-producing cells. Here, we asked whether an elevation in Rad51 levels influences the extent of viral gene transcription in astrocytic cells. Our results demonstrate that ectopic expression of Rad51 enhances the basal- and the Tat-induced transcription of the LTR promoter. This event requires cooperativity from the C/EBP family of transcription factors including C/EBPbeta and C/EBPbeta homologous protein (CHOP). Similar to Tat, we showed that Rad51 interacts with C/EBPbeta and augments its interaction with the DNA motif spanning nucleotides -120 to -94 of the LTR. Interestingly, Tat exhibited the capacity to augment the synergism between Rad51 and C/EBPbeta. Our results also demonstrate that the level of activation of the LTR by CHOP and Tat, either alone or together, is elevated in the presence of the SW1/SNF1 chromatin remodeling complex. These observations unravel a new pathway for Tat activation of the LTR that includes the positive feedback loop involving Rad51 and C/EBPbeta family proteins.

Published 3 April 2006 in J Cell Physiol, 207(3): 605-13.
Full-text of this article is available online (may require subscription).

© 2004-2008 HIV Research Today. All Rights Reserved.