H5N1亚型禽流感病毒基因重排后毒力的变化

Virulence Changes of H5N1 Avian Influenza Virus after Gene Reassortment

摘要:

【目的】为了探讨高致病性禽流感病毒对水禽致病性差异的分子致病机理。【方法】我们对从野鸭分离到的H5N1亚型禽流感病毒的生物学特性进行鉴定，其中A/mallard/Huadong/Y/2003(Y)是对麻鸭无致病性病毒，而 A/mallard/Huadong/S/2005(S)是对麻鸭高致病性病毒。利用反向遗传技术构建一系列单个和多个基因组合替换基因重排病毒，并验证重排病毒在麻鸭上的致病力。【结果】研究表明，PB2, PB1, PA(3P), HA单基因以及3P基因组合替换的使S病毒对麻鸭的毒力完全致弱，但相应的基因替换后仅使Y病毒对麻鸭的毒力略有上升。两病毒的其它基因对毒力影响较小。【结论】H5N1亚型禽流感病毒对麻鸭的致病力受多基因调控，且这种调控作用在不同病毒骨架上的影响不一致，强毒受影响程度远比弱毒的大。

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.