Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction.
Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction.
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DOI：
10.1038/cmi.2010.25
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发表时间：
2010-07
影响因子：
24.1
通讯作者：
中科院分区：
文献类型：
--
作者：
历史上，流感大流行是由禽流感病毒引起的。禽流感病毒H5 N1和H9 N2是潜在的大流行候选者。人类感染高致病性禽流感H5 N1病毒与超过60%的死亡率相关，这归因于细胞因子系统的失调。与季节性甲型流感亚型H1N1病毒相比，感染某些基因型H5 N1和H9 N2病毒的人巨噬细胞和上皮细胞表达显著升高的细胞因子和趋化因子水平。这种细胞因子和趋化因子过度诱导的机制尚未完全阐明。在本研究中，我们证明了自噬，一种严格调节的自我消化不需要的细胞亚组分的稳态过程，在细胞因子诱导中起作用。与H1N1和新的大流行性猪源性流感A/H1N1病毒相比，H9 N2/G1在更大程度上诱导自噬，并与细胞因子过度诱导相关。使用3-甲基腺嘌呤抑制自噬和小干扰RNA沉默自噬基因Atg 5，我们进一步表明自噬反应在流感病毒诱导的原代人血巨噬细胞CXCL 10和干扰素-α表达中起作用。我们的研究结果为禽流感病毒的致病机制提供了新的见解。
Historically, influenza pandemics have arisen from avian influenza viruses. Avian influenza viruses H5N1 and H9N2 are potential pandemic candidates. Infection of humans with the highly pathogenic avian influenza H5N1 virus is associated with a mortality in excess of 60%, which has been attributed to dysregulation of the cytokine system. Human macrophages and epithelial cells infected with some genotypes of H5N1 and H9N2 viruses express markedly elevated cytokine and chemokine levels when compared with seasonal influenza A subtype H1N1 virus. The mechanisms underlying this cytokine and chemokine hyperinduction are not fully elucidated. In the present study, we demonstrate that autophagy, a tightly regulated homeostatic process for self-digestion of unwanted cellular subcomponents, plays a role in cytokine induction. Autophagy is induced to a greater extent by H9N2/G1, in association with cytokine hyperinduction, compared with H1N1 and the novel pandemic swine-origin influenza A/H1N1 viruses. Using 3-methyladenine to inhibit autophagy and small interfering RNA to silence the autophagy gene, Atg5, we further show that autophagic responses play a role in influenza virus-induced CXCL10 and interferon-α expression in primary human blood macrophages. Our results provide new insights into the pathogenic mechanisms of avian influenza viruses.
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DOI：
10.1038/nrmicro1890
发表时间：
2008-05
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Miller S;Krijnse-Locker J
通讯作者：
Krijnse-Locker J
影响因子：
3.8
作者：
Mok, Chris K. P.;Lee, Davy C. W.;Lau, Allan S. Y.
通讯作者：
Lau, Allan S. Y.
影响因子：
5.4
作者：
Rudd, BD;Burstein, E;Lukacs, NW
通讯作者：
Lukacs, NW
影响因子：
9.4
作者：
Butt, KM;Smith, GJD;Guan, Y
通讯作者：
Guan, Y
影响因子：
32.4
作者：
Schmid D;Münz C
通讯作者：
Münz C