Research

Human cellular microRNA hsa-miR-29a interferes with viral nef protein expression and HIV-1 replication

Jasmine K Ahluwalia¹ , Sohrab Zafar Khan² , Kartik Soni¹ , Pratima Rawat² , Ankit Gupta¹ , Manoj Hariharan¹ , Vinod Scaria¹ , Mukesh Lalwani¹ , Beena Pillai¹ , Debashis Mitra² and Samir K Brahmachari¹

¹  Institute of Genomics and Integrative Biology (IGIB) CSIR, Mall Road, Delhi-110007, India

²  National Centre for Cell Science (NCCS), University of Pune campus, Ganeshkhind, Pune-411007, Maharashtra, India

author email corresponding author email

Retrovirology 2008, 5:117doi:10.1186/1742-4690-5-117

Published:	23 December 2008

Abstract

Background

Cellular miRNAs play an important role in the regulation of gene expression in eukaryotes. Recently, miRNAs have also been shown to be able to target and inhibit viral gene expression. Computational predictions revealed earlier that the HIV-1 genome includes regions that may be potentially targeted by human miRNAs. Here we report the functionality of predicted miR-29a target site in the HIV-1 nef gene.

Results

We find that the human miRNAs hsa-miR-29a and 29b are expressed in human peripheral blood mononuclear cells. Expression of a luciferase reporter bearing the nef miR-29a target site was decreased compared to the luciferase construct without the target site. Locked nucleic acid modified anti-miRNAs targeted against hsa-miR-29a and 29b specifically reversed the inhibitory effect mediated by cellular miRNAs on the target site. Ectopic expression of the miRNA results in repression of the target Nef protein and reduction of virus levels.

Conclusion

Our results show that the cellular miRNA hsa-miR29a downregulates the expression of Nef protein and interferes with HIV-1 replication.