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PubMed articles by:
Klase, Z.
Winograd, R.
Davis, J.
Kashanchi, F.
Retrovirology. 2009; 6: 18.
Published online 2009 February 16. doi: 10.1186/1742-4690-6-18.
PMCID: PMC2654423
Copyright © 2009 Klase et al; licensee BioMed Central Ltd.
HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression
Zachary Klase,1 Rafael Winograd,1 Jeremiah Davis,1 Lawrence Carpio,1 Richard Hildreth,1 Mohammad Heydarian,2 Sidney Fu,2 Timothy McCaffrey,2 Eti Meiri,3 Mila Ayash-Rashkovsky,3 Shlomit Gilad,3 Zwi Bentwich,3 and Fatah Kashanchicorresponding author1
1The Department of Microbiology, Immunology and Tropical Medicine program, The George Washington University School of Medicine, Washington, District of Columbia 20037, USA
2The Department of Biochemistry and Molecular Biology, The George Washington University School of Medicine, Washington, District of Columbia 20037, USA
3Rosetta Genomics Ltd., Rehovot, Israel
corresponding authorCorresponding author.
Zachary Klase: bcmzak/at/gwumc.edu; Rafael Winograd: rafi86/at/gwu.edu; Jeremiah Davis: jeremiahmd/at/gmail.com; Lawrence Carpio: carpioll84/at/gmail.com; Richard Hildreth: rl_hildreth/at/hotmail.com; Mohammad Heydarian: mh56/at/gwu.edu; Sidney Fu: bcmsxf/at/gwumc.edu; Timothy McCaffrey: mcc/at/gwu.edu; Eti Meiri: emeiri/at/rosettagenomics.com; Mila Ayash-Rashkovsky: mayash/at/rosettagenomics.com; Shlomit Gilad: sgilad/at/rosettagenomics.com; Zwi Bentwich: zbentwich/at/rosettagenomics.com; Fatah Kashanchi: bcmfxk/at/gwumc.edu
Received August 15, 2008; Accepted February 16, 2009.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
 
Abstract
Background
RNA interference is a gene regulatory mechanism that employs small RNA molecules such as microRNA. Previous work has shown that HIV-1 produces TAR viral microRNA. Here we describe the effects of the HIV-1 TAR derived microRNA on cellular gene expression.
Results
Using a variation of standard techniques we have cloned and sequenced both the 5' and 3' arms of the TAR miRNA. We show that expression of the TAR microRNA protects infected cells from apoptosis and acts by down-regulating cellular genes involved in apoptosis. Specifically, the microRNA down-regulates ERCC1 and IER3, protecting the cell from apoptosis. Comparison to our cloned sequence reveals possible target sites for the TAR miRNA as well.
Conclusion
The TAR microRNA is expressed in all stages of the viral life cycle, can be detected in latently infected cells, and represents a mechanism wherein the virus extends the life of the infected cell for the purpose of increasing viral replication.
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