Research
Nuclear Factor 90(NF90) targeted to TAR RNA inhibits transcriptional activation of HIV-1
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* Corresponding author: Ajit Kumar akumar@gwu.edu
- † Equal contributors
Department of Biochemistry & Molecular Biology, School of Medicine, The George Washington University, Washington D.C. USA
Retrovirology 2007, 4:41 doi:10.1186/1742-4690-4-41
Published: 12 June 2007Abstract
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.