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年龄对感染不同 H5N1 高致病性禽流感病毒的北京鸭发病机制和固有免疫反应的影响。

Effect of age on the pathogenesis and innate immune responses in Pekin ducks infected with different H5N1 highly pathogenic avian influenza viruses.

机构信息

Exotic and Emerging Avian Viral Diseases Research Unit, Southeast Poultry Research Laboratory, Agricultural Research Service, US Department of Agriculture, 934 College Station Road, Athens, GA 30605, USA.

出版信息

Virus Res. 2012 Aug;167(2):196-206. doi: 10.1016/j.virusres.2012.04.015. Epub 2012 May 15.

Abstract

The pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in domestic ducks varies between different viruses and is affected by the age of the ducks, with younger ducks presenting a more severe disease. In order to better understand the pathobiology of H5N1 HPAI in ducks including the role of host responses, 2 and 5-week-old Pekin ducks were infected with three different H5N1 HPAI viruses. Virus-induced pathology ranged from no clinical signs to severe disease and mortality, with the 2-week-old ducks being more severely affected by the more virulent viruses. However, these more virulent viruses induced higher body temperatures in the 5-week-old ducks than in the 2-week-old ducks indicating possible differences in innate immune responses. To analyze the ducks host responses to H5N1 HPAI virus infection, expression of innate immune-related genes was measured in the spleens and lungs of infected ducks at the peak of virus infection. IFN-α, RIG-I, and IL-6 RNA levels were increased in spleens regardless of the virus given and the age of the ducks, however differences were observed in the levels of up-regulation of IFN-α and RIG-I between the 2 and the 5-week-old ducks with the more virulent virus. Differences in IL-2 gene expression were also observed. In the lungs, the levels of expression of innate immune-related genes were lower than in the spleen, with mostly up-regulation of RIG-I and IL-6 and down-regulation of IFN-α and IL-2; no significant difference in expression was found between the 2 and the 5-week-old ducks. The differences observed in the innate immune responses to infection with H5N1 HPAI viruses could explain in part the differences in pathogenicity found between the 2 and 5-week-old ducks, however earlier time points after infection and additional innate immune-related genes should be examined.

摘要

H5N1 高致病性禽流感(HPAI)病毒在家禽鸭中的致病性因病毒不同而有所差异,且受鸭龄的影响,幼鸭的疾病更为严重。为了更好地了解 H5N1 HPAI 在鸭中的发病机制,包括宿主反应的作用,我们用三种不同的 H5N1 HPAI 病毒感染了 2 周龄和 5 周龄的北京鸭。病毒诱导的病理学表现从无临床症状到严重疾病和死亡率不等,2 周龄鸭受更毒力病毒的影响更为严重。然而,这些更毒力的病毒在 5 周龄鸭中引起的体温升高高于 2 周龄鸭,表明可能存在先天免疫反应的差异。为了分析鸭对 H5N1 HPAI 病毒感染的宿主反应,我们在病毒感染高峰期测量了感染鸭脾脏和肺脏中先天免疫相关基因的表达。无论病毒种类和鸭龄如何,IFN-α、RIG-I 和 IL-6 的 RNA 水平在脾脏中均增加,但在 2 周龄和 5 周龄鸭中 IFN-α 和 RIG-I 的上调水平存在差异,且更毒力的病毒存在这种差异。IL-2 基因表达也存在差异。在肺脏中,先天免疫相关基因的表达水平低于脾脏,主要表现为 RIG-I 和 IL-6 的上调以及 IFN-α 和 IL-2 的下调;2 周龄和 5 周龄鸭之间的表达水平没有显著差异。对 H5N1 HPAI 病毒感染的先天免疫反应的差异部分可以解释 2 周龄和 5 周龄鸭之间发现的致病性差异,但应在感染后更早的时间点和更多的先天免疫相关基因进行检查。

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