Research

HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression

Zachary Klase¹ , Rafael Winograd¹ , Jeremiah Davis¹ , Lawrence Carpio¹ , Richard Hildreth¹ , Mohammad Heydarian² , Sidney Fu² , Timothy McCaffrey² , Eti Meiri³ , Mila Ayash-Rashkovsky³ , Shlomit Gilad³ , Zwi Bentwich³ and Fatah Kashanchi¹

¹  The Department of Microbiology, Immunology and Tropical Medicine program, The George Washington University School of Medicine, Washington, District of Columbia 20037, USA

²  The Department of Biochemistry and Molecular Biology, The George Washington University School of Medicine, Washington, District of Columbia 20037, USA

³  Rosetta Genomics Ltd., Rehovot, Israel

author email corresponding author email

Retrovirology 2009, 6:18doi:10.1186/1742-4690-6-18

Published:	16 February 2009

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.