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 leavi ng less of this crucial protein to bind to and activate the natural transcr iptional promoter of HIV-1. Previous TAR decoy constructs have used HIV-I T AR. However, recent epidemiological and biological data began to suggest th at the TAR region from the human immunodeficiency virus type 2 (HIV-2) may suppress HIV-1 transcription and hence replication. We created a vector whi ch 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 inhi bits 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 d ecoy may prove useful for combating HIV-1 infection.