Influenza A virus-induced downregulation of miR-26a contributes to reduced IFNα/β production

Innate immunity provides immediate defense against viral infection. Influenza A virus(IAV) is able to get past the first line of defense. Elucidation of the molecular interaction between influenza factors and the newly recognized host players in the innate response might help in our understanding of the root causes of virulence and pathogenicity of IAV. In this study, we show that expression of miR-26 a leads to a significant inhibition of IAV replication. miR-26 a does not directly target IAV genome. Instead, miR-26 a activates the type I interferon(IFN) signaling pathway and promotes the production of IFN-stimulated genes, thus suppressing viral replication. Furthermore,ubiquitin-specific protease 3(USP3), a negative regulator of type I IFN pathway, is targeted by miR-26 a upon IAV challenge. However, miR-26 a is significantly downregulated during IAV infection.Thus, downregulation of miR-26 a is a new strategy evolved by IAV to counteract cellular antiviral responses. Our findings indicate that delivery of miR-26 a may be a potential strategy for anti-IAV therapies.

Silencing suppressors:viral weapons for countering host cell defenses

RNA silencing is a conserved eukaryotic pathway involved in the suppression of gene expression via sequence-specific interactions that are mediated by 21–23 nt RNA molecules.During infection,RNAi can act as an innate immune system to defend against viruses.As a counter-defensive strategy,silencing suppressors are encoded by viruses to inhibit various stages of the silencing process.These suppressors are diverse in sequence and structure and act via different mechanisms.In this review,we discuss whether RNAi is a defensive strategy in mammalian host cells and whether silencing suppressors can be encoded by mammalian viruses.We also review the modes of action proposed for some silencing suppressors.