Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages.
Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages.
复制标题
DOI：
10.1371/journal.pone.0008072
复制
发表时间：
2009-12-14
期刊：
影响因子：
3.7
通讯作者：
Peiris JS
中科院分区：
文献类型：
--
作者：
Lee SM;Gardy JL;Cheung CY;Cheung TK;Hui KP;Ip NY;Guan Y;Hancock RE;Peiris JS
由高致病性禽流感 (HPAI) H5N1 引起的人类疾病可导致快速进展的病毒性肺炎，从而导致急性呼吸窘迫综合征。越来越多的临床、动物模型和体外数据证据表明，病毒诱导的细胞因子失调在人类 H5N1 疾病的发病机制中发挥着重要作用。病毒在肺部的关键靶细胞是肺泡上皮和肺泡巨噬细胞，我们已经证明，与季节性人类流感病毒相比，同等感染剂量的 H5N1 病毒在体外显着上调两种原代细胞类型中的促炎细胞因子。这种 H5N1 诱导的宿主反应失调是由季节性流感病毒之间的定性（即响应 H5N1 的独特宿主途径的激活）还是定量差异驱动的，目前尚不清楚。在这里，我们使用微阵列分析和比较人原代巨噬细胞在感染H5N1病毒或低致病性季节性甲型流感（H1N1）病毒后1、3和6小时的基因表达谱。我们发现宿主对这两种病毒的反应在性质上相似，激活了几乎相同的生物过程和途径。然而，与季节性 H1N1 病毒相比，H5N1 感染会引发数量上更强的宿主炎症反应，包括 I 型干扰素 (IFN) 和肿瘤坏死因子 (TNF)-α 基因。基于网络的分析表明，IFN-β和TNF-α之间的协同作用可导致病毒感染早期增强且持续的IFN和促炎细胞因子反应，这可能有助于病毒发病机制，这与H5N1诱导的呼吸道疾病的新型治疗策略的设计相关。
Human disease caused by highly pathogenic avian influenza (HPAI) H5N1 can lead to a rapidly progressive viral pneumonia leading to acute respiratory distress syndrome. There is increasing evidence from clinical, animal models and in vitro data, which suggests a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. The key target cells for the virus in the lung are the alveolar epithelium and alveolar macrophages, and we have shown that, compared to seasonal human influenza viruses, equivalent infecting doses of H5N1 viruses markedly up-regulate pro-inflammatory cytokines in both primary cell types in vitro. Whether this H5N1-induced dysregulation of host responses is driven by qualitative (i.e activation of unique host pathways in response to H5N1) or quantitative differences between seasonal influenza viruses is unclear. Here we used microarrays to analyze and compare the gene expression profiles in primary human macrophages at 1, 3, and 6 h after infection with H5N1 virus or low-pathogenic seasonal influenza A (H1N1) virus. We found that host responses to both viruses are qualitatively similar with the activation of nearly identical biological processes and pathways. However, in comparison to seasonal H1N1 virus, H5N1 infection elicits a quantitatively stronger host inflammatory response including type I interferon (IFN) and tumor necrosis factor (TNF)-α genes. A network-based analysis suggests that the synergy between IFN-β and TNF-α results in an enhanced and sustained IFN and pro-inflammatory cytokine response at the early stage of viral infection that may contribute to the viral pathogenesis and this is of relevance to the design of novel therapeutic strategies for H5N1 induced respiratory disease.
登录
查看更多内容
DOI：
10.1210/me.2007-0153
发表时间：
2007-12
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Horsch K;de Wet H;Schuurmans MM;Allie-Reid F;Cato AC;Cunningham J;Burrin JM;Hough FS;Hulley PA
通讯作者：
Hulley PA
影响因子：
6.4
作者：
Lee, Suki M. Y.;Cheung, Chung-Yan;Peiris, J. S. Malik
通讯作者：
Peiris, J. S. Malik
影响因子：
32.4
作者：
Chong, MMW;Cornish, AL;Kay, TWH
通讯作者：
Kay, TWH
影响因子：
4.8
作者：
Clark, Kristopher;Plater, Lorna;Cohen, Philip
通讯作者：
Cohen, Philip
影响因子：
16
作者：
Cheng, EHYA;Wei, MC;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ