Virulence Changes of H5N1 Avian Influenza Virus after Gene Reassortment

Abstract:

[Objective] Recently H5N1 subtype avian influenza virus (AIV) is capable of mortality to aquatic bird. The molecular basis for the virulence of this virus is still poorly understood. [Methods] We characterized two H5N1 subtype viruses, A/mallard/Huadong/Y/2003 (Y) is nonpathogenic to mallard whereas A/mallard/Huadong/S/2005 (S) is highly pathogenic to mallard. Using reverse genetics, we constructed a series of single-gene or multiple-gene reassortants from these two viruses. [Results] Substitution of single-gene for PB2, PB1, PA (3P), HA and of combination for 3P gene resulted in complete attenuation of S virus in mallard. However, these corresponding substitutions only slightly increased virulence of Y virus in mallard. Other gene segments had little contribution to the virulence of both viruses. [Conclusion] These results indicate that the pathogenicity of H5N1 AIV to mallard was regulated by multiple gene segments, and these regulations had more sensitive effect on highly pathogenic virus backbone than on low pathogenic virus backbone.