Active NF-κB signalling is a prerequisite for influenza virus infection
Active NF-κB signalling is a prerequisite for influenza virus infection
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DOI：
10.1099/vir.0.79958-0
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发表时间：
2004-08-01
影响因子：
3.8
通讯作者：
Mautner, J
中科院分区：
文献类型：
--
作者：
Nimmerjahn, F;Dudziak, D;Mautner, J
流感病毒仍然对人类健康构成重大威胁。尽管开展了广泛的疫苗接种计划并开发了针对基本病毒蛋白的药物，但流感病毒极高的突变率仍导致出现新的致病病毒株。因此，已经表明，流感病毒感染所必需的细胞辅因子可能是抗病毒治疗的更好靶点。先前已经报道，流感病毒有效地感染EB病毒永生化的B细胞，而伯基特淋巴瘤细胞实际上对感染具有抗性。使用这种细胞系统，这里已经表明，活性NF-κ B信号传导途径是流感病毒感染人类细胞的一般先决条件。具有低NF-κ B活性的细胞对流感病毒感染具有抗性，但在NF-κ B活化后变得敏感。此外，NF-κ B活化的阻断严重损害了流感病毒对其他高度易感细胞的感染，包括人肺癌细胞系A549和U1752以及原代人细胞。另一方面，感染牛痘。病毒不依赖于活性NF-κ B信号通路，证明了该通路对流感病毒感染的特异性。这些结果可能对开发新的抗病毒疗法和了解流感病毒生物学具有重要意义。
Influenza virus still poses a major threat to human health. Despite widespread vaccination programmes and the development of drugs targeting essential viral proteins, the extremely high mutation rate of influenza virus still leads to the emergence of new pathogenic virus strains. Therefore, it has been suggested that cellular cofactors that are essential for influenza virus infection might be better targets for antiviral therapy. It has previously been reported that influenza virus efficiently infects Epstein-Barr virus-immortalized B cells, whereas Burkitt's lymphoma cells are virtually resistant to infection. Using this cellular system, it has been shown here that an active NF-kappaB signalling pathway is a general prerequisite for influenza virus infection of human cells. Cells with low NF-kappaB activity were resistant to influenza virus infection, but became susceptible upon activation of NF-kappaB. In addition, blocking of NF-kappaB activation severely impaired influenza virus infection of otherwise highly susceptible cells, including the human lung carcinoma cell lines A549 and U1752 and primary human cells. On the other hand, infection with vaccinia. virus was not dependent on an active NF-kappaB signalling pathway, demonstrating the specificity of this pathway for influenza virus infection. These results might be of major importance for both the development of new antiviral therapies and the understanding of influenza virus biology.