Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells.
Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells.
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趋化性抗病毒细胞因子促进了人腺病毒的传染性根尖进入偏振上皮细胞。
DOI：
10.1038/ncomms1391
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发表时间：
2011-07-12
影响因子：
16.6
通讯作者：
Greber UF
中科院分区：
文献类型：
--
作者：
Lütschg V;Boucke K;Hemmi S;Greber UF
粘膜上皮对病原体提供了强大的屏障。例如，极化上皮细胞向外的顶膜缺乏对诸如丙型肝炎病毒、疱疹病毒、呼肠孤病毒、脊髓灰质炎病毒或腺病毒等病原体的受体。此外，巨噬细胞从腔隙中清除病原体。在这里，我们表明人类腺病毒5型参与抗病毒免疫反应进入极化上皮细胞。血源性巨噬细胞在极化上皮细胞顶端共培养，促进上皮细胞感染。如果含有趋化细胞因子CXCL8（白细胞介素-8）或重组CXCL8的病毒条件巨噬细胞培养基存在，在没有巨噬细胞的情况下也会发生感染。在极化细胞中，CXCL8通过顶端CXCR1和CXCR2受体激活src家族酪氨酸激酶。这一激活过程将病毒共受体ανβ3整合素重新定位到根尖表面，并使根尖结合和感染腺病毒依赖于初级腺病毒受体CAR。这种模式可以解释其他粘膜病原体是如何进入上皮细胞的。本文的在线版本（doi:10.1038/ncomms1391）包含补充材料，可供授权用户使用。研究病原体如何进入极化上皮细胞对理解感染很重要。在这里，上皮细胞顶膜上的趋化因子受体的激活被证明参与Src家族酪氨酸信号传导，导致病毒共受体αvβ3重新定位到顶膜和腺病毒进入。本文的在线版本（doi:10.1038/ncomms1391）包含补充材料，可供授权用户使用。
Mucosal epithelia provide strong barriers against pathogens. For instance, the outward facing apical membrane of polarized epithelial cells lacks receptors for agents, such as hepatitis C virus, herpesvirus, reovirus, poliovirus or adenovirus. In addition, macrophages eliminate pathogens from the luminal space. Here we show that human adenovirus type 5 engages an antiviral immune response to enter polarized epithelial cells. Blood-derived macrophages co-cultured apically on polarized epithelial cells facilitate epithelial infection. Infection also occurs in the absence of macrophages, if virus-conditioned macrophage-medium containing the chemotactic cytokine CXCL8 (interleukin-8), or recombinant CXCL8 are present. In polarized cells, CXCL8 activates a Src-family tyrosine kinase via the apical CXCR1 and CXCR2 receptors. This activation process relocates the viral co-receptor ανβ3 integrin to the apical surface, and enables apical binding and infection with adenovirus depending on the primary adenovirus receptor CAR. This paradigm may explain how other mucosal pathogens enter epithelial cells. The online version of this article (doi:10.1038/ncomms1391) contains supplementary material, which is available to authorized users. Studying how pathogens enter polarized epithelial cells is important for understanding infection. Here, activation of chemokine receptors on the apical membrane of epithelial cells, is shown to engage Src family tyrosine signalling, resulting in relocation of the viral co-receptor αvβ3 to the apical membrane and adenovirus entry. The online version of this article (doi:10.1038/ncomms1391) contains supplementary material, which is available to authorized users.
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影响因子：
6.4
作者：
Di Cioccio, V;Strippoli, R;Bertini, R
通讯作者：
Bertini, R
DOI：
10.1165/ajrcmb.25.2.4327
发表时间：
2001-08-01
影响因子：
6.4
作者：
Conron, M;Bondeson, J;Foxwell, BMJ
通讯作者：
Foxwell, BMJ
影响因子：
4.2
作者：
Higginbotham, JN;Seth, P;Ramsey, WJ
通讯作者：
Ramsey, WJ
影响因子：
82.9
作者：
Kuba K;Imai Y;Rao S;Gao H;Guo F;Guan B;Huan Y;Yang P;Zhang Y;Deng W;Bao L;Zhang B;Liu G;Wang Z;Chappell M;Liu Y;Zheng D;Leibbrandt A;Wada T;Slutsky AS;Liu D;Qin C;Jiang C;Penninger JM
通讯作者：
Penninger JM
影响因子：
20.3
作者：
Ballana, Ester;Pauls, Eduardo;Este, Jose A.
通讯作者：
Este, Jose A.