Inhibition of HIV-1 replication by 5'LTR decoy RNA

Abstract

Long terminal repeats (5'-LTR) contain essential enhancer and promoter elements that act as targets for cellular and viral regulatory proteins. The interplay of these cis-acting sequences with specific transcription factors (NF kappa B, Ap1, and Sp1) present in infected cells determines the rate of transcription initiation from the 5'-LTR promoter element, and thus strongly influences the level of viral replication. Furthermore, Tat functions to enhance transcriptional elongation by binding to the trans-activation response element (TAR). These transcriptional factors enhance the transcriptional elongation from the HIV-1 promoter. HIV-1 genomic RNA packaging is a highly specific process involving interactions between the viral Gag precursor and cis acting packaging signals in the 5' leader sequence of HIV-1 genomic RNA. We examined the suppression effect of HIV-1 expression by the decoy RNAs targeted to these HIV-1 transcriptional and packaging regulatory regions. HIV-1 expression was inhibited by the 5'-LTR decoy RNA, and measured by the amount of HIV-1 gag p24 protein, but no inhibition of HIV-1 packaging could be detected.