|United States Of America||Published Application||20170130229||05/11/2017||2012-597|
|Patent Cooperation Treaty||Published Application||2015195881||12/23/2015||2012-597|
This work identifies a physiological role for the Influenza A virus RNAi suppressor protein NS1 in the inhibition of specific host miRNA function.
Influenza A virus causes seasonal infections and periodic pandemics in humans and is a major public health concern. The viral pathogenesis requires expression of its multifunctional non-structural protein 1 (NS1), which inhibits the interferon response and binds dsRNA in vitro. NS1 also suppresses experimentally induced RNAi, but a physiological role for this activity is unknown. Here we show that NS1 interferes with the biogenesis of specific cellular miRNAs by direct binding to the structured miRNA precursors in infected human cells. Expression of NS1 is associated with depletion of specific precursor miRNA that have important cellular and/or immune functions, our findings indicate a role for viral suppression of RNAi in the influenza virus pathogenesis and specific methods for the treatment or inhibition of influenza infection.
Purple-and-green conjugates of peptides and double-stranded RNA target cell-surface receptors (purple) and deliver double-stranded RNA to the Dicer enzyme (orange), which cuts the RNA to the right size for RNA interference.