title: Human influenza is more effective than avian influenza at antiviral suppression in airway cells.
abstract: Airway epithelial cells are the initial site of infection with influenza viruses. The innate immune responses of airway epithelial cells to infection are important in limiting virus replication and spread. However, relatively little is known about the importance of this innate antiviral response to infection. Avian influenza viruses are a potential source of future pandemics; therefore, it is critical to examine the effectiveness of the host antiviral system to different influenza viruses. We used a human influenza (H3N2) and a low-pathogenic avian influenza (H11N9) to assess and compare the antiviral responses of Calu-3 cells. After infection, H3N2 replicated more effectively than the H11N9 in Calu-3 cells. This was not due to differential expression of sialic acid residues on Calu-3 cells, but was attributed to the interference of host antiviral responses by H3N2. H3N2 induced a delayed antiviral signaling and impaired type I and type III IFN induction compared with the H11N9. The gene encoding for nonstructural (NS) 1 protein was transfected into the bronchial epithelial cells (BECs), and the H3N2 NS1 induced a greater inhibition of antiviral responses compared with the H11N9 NS1. Although the low-pathogenic avian influenza virus was capable of infecting BECs, the human influenza virus replicated more effectively than avian influenza virus in BECs, and this was due to a differential ability of the two NS1 proteins to inhibit antiviral responses. This suggests that the subversion of human antiviral responses may be an important requirement for influenza viruses to adapt to the human host and cause disease.
authors: Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, the University of Newcastle, Newcastle, NSW, Australia.
authors: Alan Chen-Yu
authors: AC
authors: Hsu
authors: Ian
authors: I
authors: Barr
authors: Philip M
authors: PM
authors: Hansbro
authors: Peter A
authors: PA
authors: Wark
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001717:Birds; D001980:Bronchi / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D005585:Influenza in Birds / Q000378:metabolism* / Q000821:virology*; D007251:Influenza, Human / Q000378:metabolism* / Q000821:virology*; D007668:Kidney / Q000821:virology
chemical_list: D000998:Antiviral Agents