Regulation of host gene expression by HIV-1 TAR microRNAs.
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.
Department of Molecular and Cellular Biology, Beckman Research Institute at City of Hope, 1500 E Duarte Road, Duarte, CA 91010, USA.
Dominique L
DL
Ouellet
Jimmy
J
Vigneault-Edwards
Kevin
K
Létourneau
Lise-Andrée
LA
Gobeil
Isabelle
I
Plante
John C
JC
Burnett
John J
JJ
Rossi
Patrick
P
Provost
D017209:Apoptosis; D005786:Gene Expression Regulation; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D014779:Virus Replication
D035683:MicroRNAs