Human intestinal epithelial cells are susceptible to influenza virus subtype H9N2
Human intestinal epithelial cells are susceptible to influenza virus subtype H9N2
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人肠上皮细胞对H9N2流感病毒敏感
DOI：
10.1016/j.virusres.2011.09.007
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发表时间：
2012-01-01
期刊：
影响因子：
5
通讯作者：
Xing, Zheng
中科院分区：
文献类型：
--
作者：
Qu, Bingqian;Li, Xue;Xing, Zheng
禽流感病毒（Avian influenza virus，AIV）在禽类肠道内高效复制，病毒脱落是禽流感病毒在禽类间传播和从禽类向其他物种传播的关键。在这项研究中，我们发现从人类患者中分离的H9 N2病毒株引起典型的流感样症状和疾病，包括Balb/c小鼠的体重减轻，并且可以在肠道组织中检测到病毒RNA。我们证明，人肠上皮细胞系HT-29对该病毒敏感，并且感染后的细胞在早期阶段发生凋亡。与2009年H1N1流感分离株相比，我们发现人H9 N2病毒诱导了更严重的凋亡和更强的先天免疫应答。在人肠上皮细胞中，外源性和内源性凋亡途径都被激活，并且响应于H9 N2感染，FasL和TNF-α的水平被诱导高达数百倍。有趣的是，Bcl-2家族成员Bid在感染过程中被切割，并且截短的Bid（tBid）似乎在内在凋亡的启动中起作用，细胞质中细胞色素c的释放增加。在H9 N2感染的肠上皮细胞中，RANTES和IP 10被显著诱导，并可能在肠道致病性中发挥主要作用。此外，TLR-8、MyD 88和MDA-5在感染中均上调，这在诱导IFN-β和宿主对H9 N2病毒的先天免疫中至关重要。我们的研究结果表明，人类肠道对H9 N2亚型流感病毒的反应具有独特的模式，这将拓宽我们对人类和动物AIV感染发病机制的理解。(C)2011 Elsevier B. V.保留所有权利。
Avian influenza viruses (AIV) replicate efficiently in guts of birds, and virus shedding is critical to viral transmission among birds and from birds to other species. In this study, we showed that an H9N2 viral strain, isolated from a human patient, caused typical influenza-like signs and illness including loss of body weight in Balb/c mice, and that viral RNA could be detected in intestinal tissues. We demonstrated that human intestinal epithelial cell line HT-29 was susceptible to the virus, and the infected cells went apoptotic at the early stage post infection. Compared to a pandemic (H1N1) 2009 influenza isolate, we found that the human H9N2 virus induced more severe apoptotic and stronger innate immune responses. Both extrinsic and intrinsic apoptotic pathways were activated in human intestinal epithelial cells, and the levels of FasL and TNF-alpha were induced up to hundreds-fold in response to the H9N2 infection. Interestingly, Bcl-2 family member Bid was cleaved during the course of infection, and the truncated Bid (tBid) appeared to play a role in the initiation of the intrinsic apoptosis with increased release of cytochrome c in cytosol. As for pro-inflammatory responses in H9N2-infected intestinal epithelial cells, RANTES and IP10 were induced significantly and may have played a major role in intestinal pathogenicity. Moreover, TLR-8, MyD88, and MDA-5 were all up-regulated in the infection, critical in the induction of IFN-beta and host innate immunity against the H9N2 virus. Our findings have demonstrated a unique pattern of host responses in human gut in response to H9N2 subtype influenza viruses, which will broaden our understanding of the pathogenesis of AIV infection in both humans and animals. (C) 2011 Elsevier B.V. All rights reserved.