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Open Access Highly Accessed Research

Regulation of host gene expression by HIV-1 TAR microRNAs

Dominique L Ouellet123, Jimmy Vigneault-Edwards23, Kevin Létourneau23, Lise-Andrée Gobeil23, Isabelle Plante23, John C Burnett1, John J Rossi1* and Patrick Provost23*

Author Affiliations

1 Department of Molecular and Cellular Biology, Beckman Research Institute at City of Hope, 1500 E Duarte Road, Duarte, CA 91010, USA

2 CHUQ Research Center/CHUL, 2705 Blvd Laurier, Quebec, QC G1V 4G2, Canada

3 Faculty of Medicine, Université Laval, Quebec, QC G1V 0A6, Canada

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Retrovirology 2013, 10:86  doi:10.1186/1742-4690-10-86

Published: 12 August 2013

Abstract

Background

The transactivating response (TAR) element of human immunodeficiency virus type 1 (HIV-1) is the source of two functional microRNAs (miRNAs), miR-TAR-5p and miR-TAR-3p. The objective of this study was to characterize the post-transcriptional regulation of host messenger RNAs (mRNAs) relevant to HIV-1 pathogenesis by HIV-1 TAR miRNAs.

Results

We demonstrated that TAR miRNAs derived from HIV-1 can incorporate into host effector Argonaute protein complexes, which is required if these miRNAs are to regulate host mRNA expression. Bioinformatic predictions and reporter gene activity assays identified regulatory elements complementary and responsive to miR-TAR-5p and miR-TAR-3p in the 3’ untranslated region (UTR) of several candidate genes involved in apoptosis and cell survival. These include Caspase 8, Aiolos, Ikaros and Nucleophosmin (NPM)/B23. Analyses of Jurkat cells that stably expressed HIV-1 TAR or contained a full-length latent HIV provirus suggested that HIV-1 TAR miRNAs could regulate the expression of genes in T cells that affect the balance between apoptosis and cell survival.

Conclusions

HIV-1 TAR miRNAs may contribute to the replication cycle and pathogenesis of HIV-1, by regulating host genes involved in the intricate balance between apoptosis and infected cell, to induce conditions that promote HIV-1 propagation and survival.

Keywords:
HIV-1; TAR microRNAs; Apoptosis; Caspase 8; Ikaros; Aiolos; Nucleophosmin (NPM)/B23