Global host immune response:: Pathogenesis and transcriptional profiling of type a influenza viruses expressing the hemagglutinin and neuraminidase genes from the 1918 pandemic virus
Global host immune response:: Pathogenesis and transcriptional profiling of type a influenza viruses expressing the hemagglutinin and neuraminidase genes from the 1918 pandemic virus
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DOI：
10.1128/jvi.78.17.9499-9511.2004
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发表时间：
2004-09-01
影响因子：
5.4
通讯作者：
Tumpey, TM
中科院分区：
文献类型：
--
作者：
Kash, JC;Basler, CF;Tumpey, TM
为了更全面地了解与高毒力或减毒流感病毒感染相关的分子事件，我们研究了1918血凝素（HA）和神经氨酸酶（NA）基因在生物安全3级（农业）条件下对病毒感染小鼠的影响。利用组织病理学和cDNA微阵列技术，我们检测了1918年流感大流行病毒HA和NA基因在重组流感病毒a/ WSN/33中与亲本a/ WSN/33病毒和表达a/新喀里多尼亚/20/99病毒HA和NA基因的减毒病毒的表达结果。与新喀里多尼亚HA/NA:WSN重组病毒相比，1918年HA/NA:WSN重组病毒对小鼠具有高致死率，并表现出严重的肺部病理。对从感染动物分离的肺组织进行的表达微阵列分析显示，许多参与炎症反应的基因被激活，包括细胞因子、细胞凋亡和淋巴细胞基因，这些基因在所有三种感染组中都是常见的。然而，与组织病理学研究一致，WSN和1918 HVNA:WSN重组病毒显示与活化T细胞和巨噬细胞相关的基因，以及与细胞凋亡、组织损伤和氧化损伤相关的基因的上调，这些基因在新喀里多尼亚HA/NA:WSN重组病毒感染的小鼠中未观察到。这些研究记录了基因表达谱的明显差异，这些差异与强毒性和减毒流感病毒感染引起的肺部疾病病理相关。
To understand more fully the molecular events associated with highly virulent or attenuated influenza virus infections, we have studied the effects of expression of the 1918 hemagglutinin (HA) and neuraminidase (NA) genes during viral infection in mice under biosafety level 3 (agricultural) conditions. Using histopathology and cDNA microarrays, we examined the consequences of expression of the HA and NA genes of the 1918 pandemic virus in a recombinant influenza A/WSN/33 virus compared to parental A/WSN/33 virus and to an attenuated virus expressing the HA and NA genes from A/New Caledonia/20/99. The 1918 HA/NA:WSN and WSN recombinant viruses were highly lethal for mice and displayed severe lung pathology in comparison to the nonlethal New Caledonia HA/NA:WSN recombinant virus. Expression microarray analysis performed on lung tissues isolated from the infected animals showed activation of many genes involved in the inflammatory response, including cytokine, apoptosis, and lymphocyte genes that were common to all three infection groups. However, consistent with the histopathology studies, the WSN and 1918 HVNA:WSN recombinant viruses showed increased up-regulation of genes associated with activated T cells and macrophages, as well as genes involved in apoptosis, tissue injury, and oxidative damage that were not observed in the New Caledonia HA/NA:WSN recombinant virus-infected mice. These studies document clear differences in gene expression profiles that were correlated with pulmonary disease pathology induced by virulent and attenuated influenza virus infections.