GENOMIC AND FUNCTIONAL ANALYSIS OF THE MUCOSAL IMMUNE RESPONSE AND ITS ROLE IN PROTECTION AGAINST RESPIRATORY PATHOGENS IN POULTRY
Location: Exotic and Emerging Avian Viral Diseases Research Unit
Title: Association of Mx1 Asn 631 variant alleles with enhanced resistance and altered cytokine response in chickens infected with a highly pathogenic avian influenza virus
Submitted to: Immunogenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 23, 2010
Publication Date: February 1, 2011
Citation: Ewald, S.J., Kapczynski, D.R., Livant, E.J., Suarez, D.L., Ralph, J., Mcleod, S., Miller, C. 2011. Association of Mx1 Asn 631 variant alleles with enhanced resistance and altered cytokine response in chickens infected with a highly pathogenic avian influenza virus. Immunogenetics. 63(6):363-375.
Interpretive Summary: Myxovirus-resistance (Mx) proteins are produced by host cells in response to Type I interferons, and some members of the Mx gene family in mammals have been shown to limit replication of influenza and other viruses. Chickens have a single Mx gene with multiple alleles. Chicken Mx1 variants encoding Asn at position 631 reportedly have antiviral activity, whereas variants with Ser at 631 lack activity in experiments evaluating Mx1 cDNA expressed ectopically in a cell line. We evaluated whether the Mx1 631 dimorphism influenced pathogenesis of highly pathogenic avian influenza virus (HPAIV) infection in chickens of two commercial broiler lines, each segregating for Asn631 and Ser631 variants. The two Mx1 631 homozygous genotypes were produced from Mx1 Asn631/Ser631 heterozygous parents for challenge with HPAIV strain A/Chicken/Queretaro/14588-19/1995 H5N2. Following intranasal infection with virus, progeny homozygous for Asn631 allele were significantly more resistant to disease based on mortality, morbidity or virus shedding than the group homozygous for Ser631 allele. Differences between the Mx1 631 variants were also seen in splenic cytokine transcripts after infection. Nucleotide sequence determination of Mx1 cDNAs demonstrated that the Asn631 variants in the two chicken lines differed at several amino acid positions outside 631. In vitro experiments with an influenza strain of low pathogenicity failed to demonstrate an effect of Mx1 Asn631 on viral replication. Overall, these studies provide the first evidence that Mx1 contributes to protection against influenza infection of chickens.
Myxovirus-resistance (Mx) proteins are produced by host cells and have been shown to limit replication of influenza and other viruses. Selective breeding for the Mx polymorphism is an attractive approach to improve genetic resistance of chickens to avian influenza (AI) viruses. Following infection with highly pathogenic AI viruses, differences in mean death time were observed between different Mx-specific chickens. In addition, differences in immune response were observed between chickens differing in the Mx gene. These results help understand the importance of this allele in overall immunity of chickens to avian influenza and other poultry viruses.