Potent inhibition of human immunodeficiency virus type 1 (HIV-1) gene expression and virus production by an HIV-2 tat activation-response RNA decoy.
Tat activation-response region (TAR) decoys have been developed for use in gene therapy for people infected with human immunodeficiency virus type 1 (HIV-1). When a TAR RNA decoy is overexpressed, it will bind Tat, thus leaving less of this crucial protein to bind to and activate the natural transcriptional promoter of HIV-1. Previous TAR decoy constructs have used HIV-1 TAR. However, recent epidemiological and biological data began to suggest that the TAR region from the human immunodeficiency virus type 2 (HIV-2) may suppress HIV-1 transcription and hence replication. We created a vector which overexpresses TAR-2 under the control of the human U6 small nuclear RNA gene promoter and here show that the U6-TAR-2 decoy construct potently inhibits both HIV-2 and HIV-1 gene expression. Further, this decoy construct is able to markedly suppress HIV-1 replication. Thus, we have directly proven that TAR-2 can suppress HIV-1 replication and suggest that the HIV-2 TAR decoy may prove useful for combating HIV-1 infection.
Browning
C M
CM
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Cagnon
L
L
Good
P D
PD
Rossi
J
J
Engelke
D R
DR
Markovitz
D M
DM
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D001426:Bacterial Proteins / Q000502:physiology*; D002628:Chemoreceptor Cells; D029968:Escherichia coli Proteins; D015870:Gene Expression; D015696:Gene Products, tat / Q000502:physiology*; D015316:Genetic Therapy; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D015498:HIV-2 / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface; D020218:Response Elements; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D015696:Gene Products, tat; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C057331:Tar protein, E coli; D054322:tat Gene Products, Human Immunodeficiency Virus