Full genome comparison and characterization of avian H10 viruses with different pathogenicity in Mink (Mustela vison) reveals genetic and functional differences in the non-structural gene

Phylogenetic analysis revealed a close relationship between the viruses studied. Our study also showed that there are no genetic differences in receptor specificity or the cleavability of the haemagglutinin proteins of these viruses regardless of whether they are of low or high pathogenicity in mink.In poly I:C stimulated mink lung cells the NS1 protein of influenza A virus showing high pathogenicity in mink down regulated the type I interferon promoter activity to a greater extent than the NS1 protein of the virus showing low pathogenicity in mink.Differences in pathogenicity and virulence in mink between these strains could be related to clear amino acid differences in the non structural 1 (NS1) protein. The NS gene of mink/84 appears to have contributed to the virulence of the virus in mink by helping the virus evade the innate immune responses.The outbreak of severe respiratory disease in mink (Mustela vison) in 1984 was linked to an avian influenza virus of subtype H10N4. At the time this was the first known outbreak of avian influenza A virus infection in a terrestrial mammalian species [1,2]. The only possible explanation was that birds carrying the virus transmitted it via their faeces to the mink. At the time, this was one of the very first cases of direct transmission of avian influenza virus to a terrestrial mammalian species [1].Only a few months after the outbreak in Swedish mink, some viruses of the H10N4 subtype were isolated from domestic and wild birds in Great Britain [3]. Rather crude full-genomic comparison by oligonucleotide (ON) mapping [4] and sequence analysis of the HA [5] and NP genes [6] were conducted. The ON mapping showed a close genomic relationship between the mink isolate (A/Mink/Sweden/3900/84) and the concomitant avian H10N4 viruses from fowl (A/fowl/Hampshire/378/85) and mallard (A/mallard/Gloucestershire/374/85) respectively, and a weaker genomic relationship with the H10 prototype [7] virus (A/chicken/Germany/N/49) [4].Experimen