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


CONCLUSIONS
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.
Klase
Zachary
Z
The Department of Microbiology, Immunology and Tropical Medicine program, The George Washington University School of Medicine, Washington, District of Columbia 20037, USA. bcmzak@gwumc.edu
Winograd
Rafael
R
Davis
Jeremiah
J
Carpio
Lawrence
L
Hildreth
Richard
R
Heydarian
Mohammad
M
Fu
Sidney
S
McCaffrey
Timothy
T
Meiri
Eti
E
Ayash-Rashkovsky
Mila
M
Gilad
Shlomit
S
Bentwich
Zwi
Z
Kashanchi
Fatah
F
D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000502:physiology*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism; D016415:Sequence Alignment; D020298:U937 Cells
D004268:DNA-Binding Proteins; D035683:MicroRNAs; C071447:ERCC1 protein, human; D004720:Endonucleases; D043244:Ribonuclease III; D053148:Caspase 3