Protection against lethal influenza virus challenge by RNA interference<i>in vivo</i>

TLDR

Influenza causes hundreds of thousands of deaths annually, and existing vaccines and antivirals offer limited protection, highlighting the need for new approaches such as RNA interference. siRNAs targeting conserved nucleoprotein or polymerase regions suppressed influenza A replication in mice, lowered lung viral loads, and conferred protection against lethal H5 and H7 challenges, demonstrating RNA interference’s potential for broad antiviral control.

Abstract

Influenza virus infection is responsible for hundreds of thousands of deaths annually. Current vaccination strategies and antiviral drugs provide limited protection; therefore, new strategies are needed. RNA interference is an effective means of suppressing virus replication in vitro . Here we demonstrate that treatment with small interfering RNAs (siRNAs) specific for highly conserved regions of the nucleoprotein or acidic polymerase inhibits influenza A virus replication in vivo . Delivery of these siRNAs significantly reduced lung virus titers in infected mice and protected animals from lethal challenge. This protection was specific and not mediated by an antiviral IFN response. Moreover, influenza-specific siRNA treatment was broadly effective and protected animals against lethal challenge with highly pathogenic avian influenza A viruses of the H5 and H7 subtypes. These results indicate that RNA interference is promising for control of influenza virus infection, as well as other viral infections.