Role of the Mx polymorphism coding for amino acid position 631 in chicken lines experimentally infected with a highly pathogenic H7N1 avian influenza virus

Mx1 protein has been implicated as major component in resistance to influenza virus in mice. The chicken Mx protein was initially reported to have no antiviral activity, however, Mx cDNAs from some chicken breeds were subsequently shown to have antiviral activity to vesicular stomatitis virus (VSV) and to H5N1 influenza virus when expressed in 3T3 cells. In particular, the substitution of Ser to Asn at position 631 of chicken Mx protein (resulting from the 2,032 G/A polymorphism of the Mx cDNA) was shown to determine the antiviral activity to VSV. We carried out experimental infection of five lines of chicken with a HPAI H7N1 virus to analyse the effect of the 2,032 Mx polymorphism on the response to infection. A total of 85 birds were infected with a dose of 103EID50/bird of H7N1 A/chicken/Italy/13474/99. Different responses to the infection were observed: in particular, two lines showed some degree of resistance with 35% and 73% of birds surviving the 21-day trial and remaining healthy. The Mx 2,032 polymorphism was genotyped by sequencing and PCR-RFLP. The results indicated that there was no significant association between Mx genotype at position 2,032 and either the survival rate or how long a bird remains healthy after viral inoculation. However, the chicken line had a significant effect on the survival time. It is thus necessary to analyse the complete chicken Mx gene before the role of this gene in resistance to avian influenza (AI) can be excluded. It is likely that in addition to Mx gene many other factors are involved in resistance/susceptibility of chicken to the virus. In conclusion, this study suggests that there is genetically controlled variation in response to AI virus challenge and analysis of genetic mechanisms controlling resistance to AI virus will be valuable to reducing the threat of AI in poultry on human health.