title: The effect of avian influenza virus NS1 allele on virus replication and innate gene expression in avian cells.
abstract: The NS1 gene encoded by Type A influenza virus circulates as two alleles, the A and B allele. The immunomodulatory properties of the NS1 A allele have been thoroughly examined; however, comparisons of allele function have been predominantly made in mammalian systems. Here we show that counter to the current understanding of allele function in mammals, the two alleles similarly regulate elements of the type I interferon (IFN) signaling pathway, including the interferon-inducible genes Mx and 2'-5' oligoadenylate synthase (2'-5' OAS), and IL-6, which share the same induction pathway as the interferons in embryo fibroblasts from chickens, turkeys or ducks. Replication of two reassortant viruses demonstrated that the B allele virus replicates more and to higher titers than the A allele virus in duck cells; however, the A allele virus replicates more in the cells from chickens and turkeys. Finally, chimeric constructs were used to identify a region of the NS1 gene that conferred the statistically significant differences in expression and replication observed between the alleles.
authors.affiliation: Department of Population Health and Reproduction, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Adams
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xing
authors.forename: Jinling
authors.initials: J
authors.lastname: Li
authors.forename: Kristelle
authors.initials: K
authors.lastname: Mendoza
authors.forename: Daniel
authors.initials: D
authors.lastname: Perez
authors.forename: Kent
authors.initials: K
authors.lastname: Reed
authors.forename: Carol
authors.initials: C
authors.lastname: Cardona
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D004372:Ducks; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000235:genetics; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D007370:Interferon Type I / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008969:Molecular Sequence Data; D064547:Myxovirus Resistance Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics; D014422:Turkeys; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*
chemical_list: D030161:Avian Proteins; C085820:INS1 protein, influenza virus; D007370:Interferon Type I; D015850:Interleukin-6; D064547:Myxovirus Resistance Proteins; D017361:Viral Nonstructural Proteins; D015088:2',5'-Oligoadenylate Synthetase
keywords: 2′–5′ OAS; AIV; Avian influenza virus; CEF; Cytokine expression; DEF; Interferon; Mx; NS1; NS1 protein; TEF; avian influenza virus; chicken embryo fibroblasts; duck embryo fibroblasts; non-structural 1; nt; nucleotide; turkey embryo fibroblasts; vRNA; viral ribonucleic acid