Regulation of host gene expression by HIV-1 TAR microRNAs

Retrovirology

Patrick Provost¹  John J Rossi²  John C Burnett²  Isabelle Plante¹  Lise-Andrée Gobeil¹  Kevin Létourneau¹  Jimmy Vigneault-Edwards¹  Dominique L Ouellet¹ 

[1] Faculty of Medicine, Université Laval, Quebec, QC G1V 0A6, Canada;Department of Molecular and Cellular Biology, Beckman Research Institute at City of Hope, 1500 E Duarte Road, Duarte, CA 91010, USA

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

Others  :  1209082
DOI  :  10.1186/1742-4690-10-86

 received in 2013-06-22, accepted in 2013-08-06,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Ouellet et al.; licensee BioMed Central Ltd.

【 图 表 】

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