Integrin αvβ5 Internalizes Zika Virus during Neural Stem Cells Infection and Provides a Promising Target for Antiviral Therapy.,Cell Reports

当前位置： X-MOL 学术 › Cell Rep. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Integrin αvβ5 Internalizes Zika Virus during Neural Stem Cells Infection and Provides a Promising Target for Antiviral Therapy.
Cell Reports ( IF 7.5 ) Pub Date : 2020-01-16 , DOI: 10.1016/j.celrep.2019.11.020
Shaobo Wang ₁ , Qiong Zhang ₁ , Shashi Kant Tiwari ₁ , Gianluigi Lichinchi ₁ , Edwin H Yau ₂ , Hui Hui ₃ , Wanyu Li ₃ , Frank Furnari ₄ , Tariq M Rana ₅

Affiliation

Division of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA.
Division of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Division of Hematology-Oncology, Department of Internal Medicine, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Division of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Department of Biology, Bioinformatics Program, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Ludwig Institute for Cancer Research, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA; Department of Pathology, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA; Moores Cancer Center, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Division of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Department of Biology, Bioinformatics Program, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA; Moores Cancer Center, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.

We perform a CRISPR-Cas9 genome-wide screen in glioblastoma stem cells and identify integrin αvβ5 as an internalization factor for Zika virus (ZIKV). Expression of αvβ5 is correlated with ZIKV susceptibility in various cells and tropism in developing human cerebral cortex. A blocking antibody against integrin αvβ5, but not αvβ3, efficiently inhibits ZIKV infection. ZIKV binds to cells but fails to internalize when treated with integrin αvβ5-blocking antibody. αvβ5 directly binds to ZIKV virions and activates focal adhesion kinase, which is required for ZIKV infection. Finally, αvβ5 blocking antibody or two inhibitors, SB273005 and cilengitide, reduces ZIKV infection and alleviates ZIKV-induced pathology in human neural stem cells and in mouse brain. Altogether, our findings identify integrin αvβ5 as an internalization factor for ZIKV, providing a promising therapeutic target, as well as two drug candidates for prophylactic use or treatments for ZIKV infections.

中文翻译：

整联蛋白αvβ5在神经干细胞感染期间内化了寨卡病毒，并为抗病毒治疗提供了有希望的靶标。

我们在胶质母细胞瘤干细胞中进行了CRISPR-Cas9全基因组筛选，并将整联蛋白αvβ5鉴定为寨卡病毒（ZIKV）的内在化因子。αvβ5的表达与ZIKV在各种细胞中的易感性以及人类大脑皮层发育的向性相关。针对整联蛋白αvβ5（而非αvβ3）的封闭抗体可有效抑制ZIKV感染。ZIKV与细胞结合，但在用整联蛋白αvβ5阻断抗体处理时无法内在化。αvβ5直接结合ZIKV病毒体并激活粘着斑激酶，这是ZIKV感染所必需的。最后，αvβ5阻断抗体或两种抑制剂SB273005和cilengitide可以减少ZIKV感染并减轻ZIKV诱导的人神经干细胞和小鼠脑部病变。总之，我们的发现确定整联蛋白αvβ5是ZIKV的内在化因子，

更新日期：2020-01-17

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11