Modeling host responses in ferrets during A/California/07/2009 influenza infection.

Modeling host responses in ferrets during A/California/07/2009 influenza infection.
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DOI:
10.1016/j.virol.2010.02.020
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发表时间:
2010-06-05
期刊:
影响因子:
3.7
通讯作者:
Ross TM
Ross TM
中科院分区:
医学3区
文献类型:
--
作者:
Rowe T;León AJ;Crevar CJ;Carter DM;Xu L;Ran L;Fang Y;Cameron CM;Cameron MJ;Banner D;Ng DC;Ran R;Weirback HK;Wiley CA;Kelvin DJ;Ross TM

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感染2009年H1N1流感大流行病毒(2009-H1N1)时的免疫反应仍然知之甚少。利用实验感染模型,研究了2009-H1N1 A/California/07/2009和季节性A/Brisbane/59/2007感染雪貂的病理特征和宿主免疫反应。趋化因子CCL2、CCL8、CXCL7和CXCL10以及大多数干扰素刺激基因在感染A/California/07/2009后的第7天早期表达,并与肺部病理相关,表达突然下降。有趣的是,先天免疫基因表达的下降被颗粒酶和免疫球蛋白的适应性免疫基因的显著增加所取代。第7天首次观察到血清抗流感抗体,与病毒清除率相当。我们认为,人类肺部病理发生在宿主免疫的先天期,延迟或未能转换到适应期可能导致2009-H1N1严重感染期间的发病率和死亡率。
Immune responses during infection with pandemic H1N1 2009 influenza A virus (2009-H1N1) are still poorly understood. Using an experimental infection model in ferrets, we examined the pathological features and characterized the host immune responses by using microarray analysis, during infection with 2009-H1N1 A/California/07/2009 and seasonal A/Brisbane/59/2007. Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of interferon-stimulated genes were expressed early, correlated to lung pathology, and abruptly decreased expression on day 7 following infection of A/California/07/2009. Interestingly, the drop in innate immune gene expression was replaced by a significant increase of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-influenza antibodies were first observed on day 7, commensurate with the viral clearance. We propose that lung pathology in humans occurs during the innate phase of host immunity and a delay or failure to switch to the adaptive phase may contribute to morbidity and mortality during severe 2009-H1N1 infections.
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