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Neutrophils Infected with highly virulent Influenza H3N2 virus exhibit augmented early cell death and rapid Induction of type I interferoe signaling pathways

机译:感染高毒力H3N2流感病毒的中性粒细胞显示出增加的早期细胞死亡和I型干扰素信号传导途径的快速诱导

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We developed a model of influenza virus infection of neutrophils by inducing differentiation of the MPRO promyelocytic cell line. After 5 days of differentiation, about 20-30% of mature neutrophils could be detected. Only a fraction of neutrophils were infected by highly virulent influenza (HVI) virus, but were unable to support active viral replication compared with MDCK cells. HVI infection of neutrophils augmented early and late apoptosis as indicated by annexin V and TUNEL assays. Comparison between the global transcriptomic responses of neutrophils to HVI and low virulent influenza (LVI) revealed that the IFN regulatory factor and IFN signaling pathways were the most significantly overrepresented pathways, with activation of related genes in HVI as early as 3 h. Relatively consistent results were obtained by real-time RT-PCR of selected genes associated with the type I IFN pathway. Early after HVI infection, comparatively enhanced expression of apoptosis-related genes was also elicited.
机译:我们通过诱导MPRO早幼粒细胞系的分化建立了嗜中性粒细胞流感病毒感染模型。分化5天后,可以检测到约20-30%的成熟中性粒细胞。与MDCK细胞相比,只有一小部分嗜中性粒细胞被高毒性流感病毒(HVI)感染,但无法支持主动病毒复制。如膜联蛋白V和TUNEL分析所示,嗜中性粒细胞的HVI感染会增加早期和晚期凋亡。中性粒细胞对HVI和低毒力流感(LVI)的整体转录反应的比较显示,IFN调节因子和IFN信号通路是最明显的代表通路,HVI中相关基因的激活最早可在3 h内完成。通过实时RT-PCR选择与I型IFN途径相关的基因获得了相对一致的结果。在HVI感染后的早期,也引起了凋亡相关基因的表达相对增强。

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