title: Mx is dispensable for interferon-mediated resistance of chicken cells against influenza A virus.
abstract: The type I interferon (IFN) system plays an important role in antiviral defense against influenza A viruses (FLUAV), which are natural chicken pathogens. Studies of mice identified the Mx1 protein as a key effector molecule of the IFN-induced antiviral state against FLUAV. Chicken Mx genes are highly polymorphic, and recent studies suggested that an Asn/Ser polymorphism at amino acid position 631 determines the antiviral activity of the chicken Mx protein. By employing chicken embryo fibroblasts with defined Mx-631 polymorphisms and retroviral vectors for the expression of Mx isoforms in chicken cells and embryonated eggs, we show here that neither the 631Asn nor the 631Ser variant of chicken Mx was able to confer antiviral protection against several lowly and highly pathogenic FLUAV strains. Using a short interfering RNA (siRNA)-mediated knockdown approach, we noted that the antiviral effect of type I IFN in chicken cells was not dependent on Mx, suggesting that some other IFN-induced factors must contribute to the inhibition of FLUAV in chicken cells. Finally, we found that both isoforms of chicken Mx protein appear to lack GTPase activity, which might explain the observed lack of antiviral activity.
authors.affiliation: Department of Veterinary Science, University Munich, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schusser
authors.forename: Antje
authors.initials: A
authors.lastname: Reuter
authors.forename: Alexander
authors.initials: A
authors.lastname: von der Malsburg
authors.forename: Nicola
authors.initials: N
authors.lastname: Penski
authors.forename: Steffen
authors.initials: S
authors.lastname: Weigend
authors.forename: Bernd
authors.initials: B
authors.lastname: Kaspers
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.forename: Sonja
authors.initials: S
authors.lastname: Härtle
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics / Q000276:immunology* / Q000821:virology; D005455:Fluorescent Antibody Technique; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D009980:Influenza A virus / Q000276:immunology*; D005585:Influenza in Birds / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D064547:Myxovirus Resistance Proteins; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms; D034622:RNA Interference; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007370:Interferon Type I; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins