Adherens junction protein nectin-4 is the epithelial receptor for measles virus.
Adherens junction protein nectin-4 is the epithelial receptor for measles virus.
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DOI：
10.1038/nature10639
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发表时间：
2011-11-02
期刊：
影响因子：
64.8
通讯作者：
Cattaneo, Roberto
中科院分区：
文献类型：
--
作者：
Muhlebach, Michael D.;Mateo, Mathieu;Sinn, Patrick L.;Pruefer, Steffen;Uhlig, Katharina M.;Leonard, Vincent H. J.;Navaratnarajah, Chanakha K.;Frenzke, Marie;Wong, Xiao X.;Sawatsky, Bevan;Ramachandran, Shyam;McCray, Paul B., Jr.;Cichutek, Klaus;von Messling, Veronika;Lopez, Marc;Cattaneo, Roberto
麻疹 (MV) 是一种通过气溶胶传播的病毒，每年影响超过 1000 万儿童，并导致约 12 万人死亡。虽然长期以来人们认为它在传播前会在呼吸道上皮细胞中复制，但最近发现它最初使用信号淋巴细胞激活分子（SLAM、CD150）作为受体来感染气道的巨噬细胞和树突状细胞。然后这些细胞穿过呼吸道上皮，将感染运送到淋巴器官，MV 在淋巴器官中剧烈复制。病毒如何以及在何处重新进入呼吸道仍不清楚。基于对病毒允许的上皮细胞系上优先表达的表面蛋白的功能分析，我们将 nectin-4（脊髓灰质炎病毒受体样 4）确定为候选宿主退出受体。这种免疫球蛋白超家族的粘附连接蛋白通过其膜远端结构域以高亲和力与病毒附着蛋白相互作用。 Nectin-4 在基底外侧感染的分化良好的原代人气道上皮片中维持 MV 进入和非细胞病变横向扩散。它在受感染的上皮细胞（包括猕猴气管的上皮细胞）中下调。虽然其他病毒利用受体进入宿主或穿过其上皮屏障，但我们认为 MV 以 nectin-4 为目标，在气道中出现。 Nectin-4 是多种癌症的细胞标记物，对正在进行的基于 MV 的溶瘤临床试验具有重要意义。
Measles (MV) is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths. While it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to initially infect macrophages and dendritic cells of the airways using the signaling lymphocytic activation molecule (SLAM, CD150) as receptor. These cells then cross the respiratory epithelium and ferry the infection to lymphatic organs where MV replicates vigorously. How and where the virus crosses back into the airways has remained unknown. Based on functional analyses of surface proteins preferentially expressed on virus-permissive epithelial cell lines, we identified nectin-4 (poliovirus-receptor-like-4) as a candidate host exit receptor. This adherens junction protein of the immunoglobulin superfamily interacts with the viral attachment protein with high affinity through its membrane-distal domain. Nectin-4 sustains MV entry and non-cytopathic lateral spread in well-differentiated primary human airway epithelial sheets infected basolaterally. It is down-regulated in infected epithelial cells, including those of macaque tracheas. While other viruses use receptors to enter hosts or transit through their epithelial barriers, we suggest that MV targets nectin-4 to emerge in the airways. Nectin-4 is a cellular marker of several types of cancer, which has implications for ongoing MV-based clinical trials of oncolysis.
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DOI：
10.1038/nrmicro1927
发表时间：
2008-07
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
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影响因子：
5.4
作者：
Leonard, Vincent H. J.;Hodge, Gregory;Cattaneo, Roberto
通讯作者：
Cattaneo, Roberto
影响因子：
64.5
作者：
MENDELSOHN, CL;WIMMER, E;RACANIELLO, VR
通讯作者：
RACANIELLO, VR
影响因子：
4.8
作者：
Navaratnarajah, Chanakha K.;Vongpunsawad, Sompong;Cattaneo, Roberto
通讯作者：
Cattaneo, Roberto
影响因子：
11.2
作者：
Galanis E;Hartmann LC;Cliby WA;Long HJ;Peethambaram PP;Barrette BA;Kaur JS;Haluska PJ Jr;Aderca I;Zollman PJ;Sloan JA;Keeney G;Atherton PJ;Podratz KC;Dowdy SC;Stanhope CR;Wilson TO;Federspiel MJ;Peng KW;Russell SJ
通讯作者：
Russell SJ