RNA interference and HIV-1: hits and misses.
OBJECTIVE
RNA interference is a type of nucleic-acid-based immunity used by cells to restrict transposons, transgenes and viruses. The RNA interference machinery targets long double-stranded RNAs to produce short RNAs that arm cellular ribonucleases to degrade foreign RNAs in a sequence-specific manner. Despite this defense, many viruses with RNA genomes, such as HIV-1, replicate seemingly unrestricted in cells. This suggests that viruses may have evolved counter-strategems that negate the host's RNA interference. We review the complex point-counterpoint RNA interference interplays between the human cells and HIV-1.


RESULTS
RNA interference functions in human cells to restrict viral replication. Recent findings suggest that HIV-1 can evade cellular RNA interference in several ways. First, the virus can mutate its sequence to evade sequence-specific targeting by RNA interference. Second, HIV-1 encodes a viral Tat protein that can partially suppress the cell's RNA interference processing machinery. Finally, HIV-1 encodes a small RNA decoy, TAR, which can sequester a cellular protein named TAR RNA binding protein. The recent discovery that TAR RNA binding protein is a required cofactor for Dicer to process microRNA and small interfering RNA suggests that TAR RNA is another moiety used by HIV-1 to defeat RNA interference.


CONCLUSIONS
We discuss stratagems used by HIV-1 and other viruses to defeat the cells' antiviral small interfering RNA/microRNA defenses. We review how viruses might control and regulate host genes by encoding viral microRNA.
aNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA bInstitut de Genetique Humaine, CNRS UPR1142, Montpellier, France.
Yamina
Y
Bennasser
Man Lung
ML
Yeung
Monsef
M
Benkirane
Kuan-Teh
KT
Jeang