TY - JOUR
T1 - HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression
AU - Klase, Zachary
AU - Winograd, Rafael
AU - Davis, Jeremiah
AU - Carpio, Lawrence
AU - Hildreth, Richard
AU - Heydarian, Mohammad
AU - Fu, Sidney
AU - McCaffrey, Timothy
AU - Meiri, Eti
AU - Ayash-Rashkovsky, Mila
AU - Gilad, Shlomit
AU - Bentwich, Zwi
AU - Kashanchi, Fatah
N1 - Funding Information:
We would like to thank Dr. Francoise Porteu of The Cochin Institute for the generous gift of the anti-IER3 antibody. We would also like to thank Drs. Rossi and Castanotto for the Pol III TAR vectors. HLM-1, cMagi and ACH2 were obtained from the NIH AIDS Reagent Program. Zachary Klase was a predoctoral student in the Immunology, Microbiology and Tropical Medicine Program of the Institute for Biomedical Sciences at the George Washington University. The current work was part of ZK dissertation Ph.D. thesis. This work was supported by grants from the George Washington University REF funds to ZK and FK; Snyder award, McCormick Grant and National Institutes of Health grants AI065236, AI043894 to FK.
PY - 2009/2/16
Y1 - 2009/2/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=62749139614&partnerID=8YFLogxK
U2 - 10.1186/1742-4690-6-18
DO - 10.1186/1742-4690-6-18
M3 - Article
C2 - 19220914
AN - SCOPUS:62749139614
VL - 6
JO - Retrovirology
JF - Retrovirology
SN - 1742-4690
M1 - 18
ER -