title: Incoming influenza A virus evades early host recognition, while influenza B virus induces interferon expression directly upon entry.
abstract: The activation of the 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 infections. Although influenza A and B viruses, which both have segmented negative-strand RNA genomes, share major structural similarities, they have evolutionarily diverged, with total genetic incompatibility. Here we compare antiviral-inducing mechanisms during infections with type A and B influenza viruses in human dendritic cells. We observed that IFN responses are induced significantly faster in cells infected with influenza B virus than in cells infected with type A influenza virus and that the early induction of antiviral gene expression is mediated by the activation of the transcription factor IFN regulatory factor 3 (IRF3). We further demonstrate that influenza A virus infection activates IFN responses only after viral RNA (vRNA) synthesis, whereas influenza B virus induces IFN responses even if its infectivity is destroyed by UV treatment. Thus, initial viral transcription, replication, and viral protein synthesis are dispensable for influenza B virus-induced antiviral responses. Moreover, vRNA molecules from both type A and B viruses are equally potent activators of IFN induction, but incoming influenza B virus structures are recognized directly in the cytosol, while influenza A virus is able to evade early recognition. Collectively, our data provide new evidence of a novel antiviral evasion strategy for influenza A virus without a contribution of the viral NS1 protein, and this opens up new insights into different influenza virus pathogenicities.
authors.affiliation: Department of Infectious Disease Surveillance and Control, Virology Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Pamela
authors.initials: P
authors.lastname: Österlund
authors.forename: Mari
authors.initials: M
authors.lastname: Strengell
authors.forename: L Peter
authors.initials: LP
authors.lastname: Sarin
authors.forename: Minna M
authors.initials: MM
authors.lastname: Poranen
authors.forename: Riku
authors.initials: R
authors.lastname: Fagerlund
authors.forename: Krister
authors.initials: K
authors.lastname: Melén
authors.forename: Ilkka
authors.initials: I
authors.lastname: Julkunen
mesh_terms: D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D004285:Dogs; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity*; D009981:Influenza B virus / Q000276:immunology* / Q000472:pathogenicity*; D007251:Influenza, Human / Q000276:immunology; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D007372:Interferons / Q000096:biosynthesis* / Q000276:immunology; D061985:Madin Darby Canine Kidney Cells; D012367:RNA, Viral / Q000096:biosynthesis; D053586:Virus Internalization
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D012367:RNA, Viral; D007372:Interferons