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Title: Polymorphism in chicken Mx gene influences susceptibility to avian influenza virus infection

item EWALD, S
item LIVANT, E
item Kapczynski, Darrell
item Suarez, David
item RALPH, J
item MCLEOD, S
item MILLER, C

Submitted to: Avian Immunology Research Group Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/20/2008
Publication Date: 6/24/2008
Citation: Ewald, S.J., Livant, E.J., Kaltenboeck, L., Kapczynski, D.R., Suarez, D.L., Ralph, J., Mcleod, S., Miller, C. 2008. Polymorphism in chicken Mx gene influences susceptibility to avian influenza virus infection [abstract]. Avian Immunology Research Group. p. 1.

Interpretive Summary:

Technical Abstract: The Mx protein is produced by host cells in response to IFN-alpha, and has been shown to confer protection against influenza in mammalian studies. Chickens have a single Mx gene with multiple alleles. In previous experiments, transfecting cDNAs of various alleles into mouse 3T3 cells, a single nucleotide polymorphism (SNP) encoding an Asn631Ser dimorphism in the Mx protein determined antiviral activity against highly pathogenic avian influenza virus (HPAIV) (Ko et al. 2002). Mx-Asn631 was antivirally positive in transfection experiments, whereas the Mx-Ser631 alleles lacked antiviral activity. We evaluated whether the Mx 631 dimorphism influenced pathogenesis of HPAIV in chickens of a commercial broiler line segregating for both Mx631 alleles. The two Mx631 homozygous genotypes were produced from heterozygous parents for challenge with HPAIV strain A/Ck/Queretaro/95. During the 10-day observation period following infection with 10^6 EID50 virus, almost all the chicks of both genotypes died; however, in the Mx-Asn631 group median survival was 4 days compared with 2 days in the Mx-Ser631 group. Analysis of cytokine transcripts in spleens 2 days post-challenge revealed that IL-1beta and IFN-alpha were significantly higher in Mx-Asn631 chicks compared with the Mx-Ser631 group. Even at a sublethal virus dose (10^4 EID50), IL-1beta and IFN-alpha'transcripts were significantly higher in spleens of Mx-Asn631 than Mx-Ser631 chicks 2 days post-challenge. Overall, these studies provide the first evidence that Mx has a role in protection against influenza infection of chickens. Supported by NRI Grant No. 2006-35205-16676 from the USDA CSREES Animal Genome Program.