Targeting to the HIV-1 RRE of the Influenza Virus NS1 Protein Effector Domain as a Potent, Specific Anti-HIV Agent

The Rev axis of HIV autoregulation is one of two critical viral regulatory pathways required for expression of viral genomic and mRNA and for replication. Consequently it is an attractive therapeutic target. Previous studies have investigated the anti-HIV efficacy of targeting to the RRE (the viral RNA target sequence of the Rev axis) a trans-dominant negative inhibitor mutant Rev, M10. In this study we have fused a portion of the influenza virus NS1 protein (which normally inhibits polyA(+) mRNA transport and splicing) to the Rev M10 gene while deleting the NS1 poly(A) binding region. The resulting chimera demonstrates specific and enhanced inhibition of viral-RRE-containing RNA expression. Copyright 1997 S. Karger AG, Basel