Short Communication: Efficiently Inhibiting HIV-1 Replication by a Prototype Foamy Virus Vector Expressing Novel H1 Promoter-Driven Short Hairpin RNAs

RNA interference has shown great potential for the treatment of HIV-1. Vectors derived from prototype foamy viruses (PFVs) with a nonpathogenic nature are very promising gene transfer vehicles in anti-HIV gene therapy. In this article, three short hairpin RNAs (shRNAs) targeting the conserved regions of the HIV-1(NL4-3) 5 ' long terminal repeat (LTR) were first designed. We then constructed novel recombinant PFV vector plasmids, p phi-H1-shRNAs, expressing these shRNAs under the control of the H1 RNA promoter. To detect the efficacy of these phi-H1-shRNAs for the inhibition of HIV-1 replication, we performed a dual-luciferase reporter assay, RT-qPCR, ELISA, western blotting, and a lactate dehydrogenase (LDH) assay by transient transfection in 293T cells. The results suggest that these novel shRNAs driven by PFV vectors inhibit HIV-1 replication efficiently without cytotoxicity, with shRNA3 being the most effective. In addition, we analyzed the shRNA target sites in the 5 ' LTR of HIV-1 strains other than HIV-1(NL4-3) and found that these shRNAs may possibly inhibit other HIV-1 strains.