191: Difference in the activation of IFN gene expression in response to influenza A and B virus entry

Abstract

Activation of interferon (IFN) system, which is triggered largely by the recognition of viral nucleic acids, is one of the most important host defense reactions against viral infection. Both influenza A and B viruses have a negative strand RNA genome and they possess significant structural similarities. However, influenza A and B viruses are evolutionally diverged with complete genetic incompatibility. We analysed the mechanisms of activation of innate immunity during the infection with type A and B influenza viruses in human dendritic cells. We have previously shown that IFN responses are induced significantly faster in cells infected with influenza B virus than type A virus. We demonstrated that influenza A virus infection activates IFN responses only after the viral RNA (vRNA) synthesis, whereas influenza B virus induces IFN responses even if the infectivity of the virus is destroyed by UV treatment. Thus, initial viral transcription, replication and viral protein synthesis are not required for influenza B virus-induced antiviral responses. Furthermore, we observed that the early induction of IFN gene expression by influenza B virus is mediated by multiple signalling pathways with strong dependency on NF-κB transcription factor in addition to IRF3. The disturbance of endosomal acidification prevented IFN induction suggesting cytosolic recognition of incoming influenza B virus structures to be important in regulating IFN gene expression. Moreover, influenza B virus NP located in the nuclei already at 15 min postinfection whereas the NP from incoming type A virus was found in nuclear fractions at later time points of infection and in significantly lesser extent. Collectively, our data provides new evidence of the mechanisms of influenza B virus recognition by the host cell providing new insights in the understanding of the pathogenesis of different influenza virus types.