An Anti-Influenza Strategy Based on siRNA Approach Targeting the Critical Viral and Host Factors

Abstract

The influenza virus remains a major public health concern causing significant morbidity and mortality in humans. Vaccination is considered the most effective prevention strategy as antivirals are suboptimal in treating the disease. Several studies have identified numerous host and viral factors utilized by the virus to successfully complete its life cycle. This study performed to investigate the effect of siRNA against two host factors, RanBP5 and CCT, and three viral proteins that make up the viral RNA polymerase (RNAP), PA, PB1, and PB2, in inhibiting the replication of diverse strains and subtypes of influenza virus. The effect of single and combinatorial siRNA on the replication of two influenza A viruses (IAV) and one influenza B virus (IBV) was evaluated in vitro in MDCK cells. siRNA against viral RNAP subunits effectively inhibits growth of both IAV and IBV. Our results further demonstrates that trafficking of the RNAP requires two host proteins, RANBP5 and CCT, with RANBP5 preferentially required for IAV and CCT required for IBV. Our results suggest that a combination of siRNA to RNAP and host import proteins is a potential prophylactic and therapeutic candidate for further development and future in vivo studies.