Research

Nuclear Factor 90(NF90) targeted to TAR RNA inhibits transcriptional activation of HIV-1

Emmanuel T Agbottah^* , Christine Traviss^* , James McArdle , Sambhav Karki , Georges C St Laurent III and Ajit Kumar

Department of Biochemistry & Molecular Biology, School of Medicine, The George Washington University, Washington D.C. USA

author email corresponding author email* Contributed equally

Retrovirology 2007, 4:41doi:10.1186/1742-4690-4-41

Published:	12 June 2007

Abstract

Background

Examination of host cell-based inhibitors of HIV-1 transcription may be important for attenuating viral replication. We describe properties of a cellular double-stranded RNA binding protein with intrinsic affinity for HIV-1 TAR RNA that interferes with Tat/TAR interaction and inhibits viral gene expression.

Results

Utilizing TAR affinity fractionation, North-Western blotting, and mobility-shift assays, we show that the C-terminal variant of nuclear factor 90 (NF90ctv) with strong affinity for the TAR RNA, competes with Tat/TAR interaction in vitro. Analysis of the effect of NF90ctv-TAR RNA interaction in vivo showed significant inhibition of Tat-transactivation of HIV-1 LTR in cells expressing NF90ctv, as well as changes in histone H3 lysine-4 and lysine-9 methylation of HIV chromatin that are consistent with the epigenetic changes in transcriptionally repressed gene.

Conclusion

Structural integrity of the TAR element is crucial in HIV-1 gene expression. Our results show that perturbation Tat/TAR RNA interaction by the dsRNA binding protein is sufficient to inhibit transcriptional activation of HIV-1.