A new Houdini act: multiple routes for HIV-1 escape from RNAi-mediated inhibition.

Evaluation of: Leonard JN, Shah PS, Burnett JC, Schaffer DV: HIV evades RNA interference directed at TAR by an indirect compensatory mechanism. Cell Host Microbe 4, 484-494 (2008). RNAi can be used to induce the silencing of messenger RNAs in a sequence-specific manner. Several therapeutic RNAi applications are actively being pursued, including the targeting of the RNA genome of human pathogenic viruses such as HIV-1. Viruses are able to escape from RNAi attack by mutation of the targeted sequence. In this report, Leonard and co-workers present evidence of a more indirect viral escape route by selection of up-mutations in the promoter that boosts viral gene expression. This indirect route may serve as a general viral evasion mechanism.