BACKGROUND Innate immunity provides first line of defense against viral infections. The interactions between hosts and influenza A virus and the response of host innate immunity to viral infection are critical determinants for the pathogenicity or virulence of influenza A viruses. This study was designed to investigate global changes of gene expression and detailed responses of innate immune systems in human and avian hosts during the course of infection with various subtypes of influenza A viruses, using collected and self-generated transcriptome sequencing data from human bronchial epithelial (HBE), human tracheobronchial epithelial (HTBE), and A549 cells infected with influenza A virus subtypes, namely H1N1, H3N2, H5N1 HALo mutant, and H7N9, and from ileum and lung of chicken and quail infected with H5N1, or H5N2. RESULTS We examined the induction of various cytokines and chemokines in human hosts infected with different subtypes of influenza A viruses. Type I and III interferons were found to be differentially induced with each subtype. H3N2 caused abrupt and the strongest response of IFN-β and IFN-λ, followed by H1N1 (though much weaker), whereas H5N1 HALo mutant and H7N9 induced very minor change in expression of type I and III interferons. Similarly, differential responses of other innate immunity-related genes were observed, including TMEM173, MX1, OASL, IFI6, IFITs, IFITMs, and various chemokine genes like CCL5, CX3CL1, and chemokine (C-X-C motif) ligands, SOCS (suppressors of cytokine signaling) genes. Third, the replication kinetics of H1N1, H3N2, H5N1 HALo mutant and H7N9 subtypes were analyzed, H5N1 HALo mutant was found to have the highest viral replication rate, followed by H3N2, and H1N1, while H7N9 had a rate similar to that of H1N1 or H3N2 though in different host cell type. CONCLUSION Our study illustrated the differential responses of innate immunity to infections of different subtypes of influenza A viruses. We found the influenza viruses which induced stronger innate immune responses replicate slower than those induces weaker innate immune responses. Our study provides important insight into links between the differential innate immune responses from hosts and the pathogenicity/ virulence of different subtypes of influenza A viruses.

中文翻译：

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人类和禽流感宿主中不同类型的甲型流感病毒触发的先天免疫的差异反应。

背景技术先天免疫为抵抗病毒感染提供了第一道防线。宿主与甲型流感病毒之间的相互作用以及宿主对病毒感染的先天免疫反应是决定甲型流感病毒致病性或致病性的关键因素。这项研究的目的是使用从人类支气管上皮细胞收集并自行生成的转录组测序数据，调查人类和禽类宿主在感染各种亚型A型流感病毒期间基因表达的全球变化以及先天免疫系统的详细反应。 HBE），人气管支气管上皮（HTBE）和A549细胞感染了甲型流感病毒亚型，即H1N1，H3N2，H5N1 HALo突变体和H7N9，并且感染了H5N1或H5N2的鸡和鹌鹑的回肠和肺。结果我们研究了感染不同亚型流感病毒亚型的人类宿主中各种细胞因子和趋化因子的诱导。发现I型和III型干扰素对每种亚型都有不同的诱导作用。H3N2引起IFN-β和IFN-λ的突变且反应最强，其次是H1N1（尽管弱得多），而H5N1 HALo突变体和H7N9引起I型和III型干扰素表达的微小变化。同样，还观察到其他与先天性免疫相关的基因的差异反应，包括TMEM173，MX1，OASL，IFI6，IFIT，IFITM和各种趋化因子基因（如CCL5，CX3CL1和趋化因子（CXC基序）配体，SOCS（细胞因子信号传导抑制剂） ）基因。第三，分析了H1N1，H3N2，H5N1 HALo突变体和H7N9亚型的复制动力学，发现H5N1 HALo突变体具有最高的病毒复制速率，其次是H3N2和H1N1，而H7N9的速率与H1N1或H3N2相似，尽管在不同的宿主细胞类型中。结论我们的研究阐明了先天免疫对不同亚型A型流感病毒感染的不同反应。我们发现，诱导更强的先天免疫反应的流感病毒复制的速度慢于诱导更弱的先天免疫反应的流感病毒的复制速度。我们的研究为宿主不同的先天免疫应答与甲型流感病毒不同亚型的致病性/毒力之间的联系提供了重要的见识。结论我们的研究阐明了先天免疫对不同亚型A型流感病毒感染的不同反应。我们发现，诱导更强的先天免疫反应的流感病毒复制的速度慢于诱导更弱的先天免疫反应的流感病毒的复制速度。我们的研究为宿主不同的先天免疫应答与甲型流感病毒不同亚型的致病性/毒力之间的联系提供了重要的见识。结论我们的研究阐明了先天免疫对不同亚型A型流感病毒感染的不同反应。我们发现，诱导更强的先天免疫反应的流感病毒复制的速度慢于诱导更弱的先天免疫反应的流感病毒的复制速度。我们的研究为宿主不同的先天免疫应答与甲型流感病毒不同亚型的致病性/毒力之间的联系提供了重要的见识。