小柯机器人

寨卡病毒通过SOX2-整合素αvβ5信号轴靶向胶质母细胞瘤干细胞，这一成果由美国加州大学圣地亚哥分校Jeremy N. Rich、David A. Cheresh、Alysson R. Muotri、Jair L. Siqueira-Neto等研究人员合作取得。2020年1月16日，《细胞—干细胞》在线发表了这项成果。

研究人员表示，寨卡病毒（ZIKV）通过杀死神经前体细胞（NPC）和其他脑细胞而引起小头畸形。ZIKV还显示出针对胶质母细胞瘤（GBM）干细胞（GSC）的治疗性溶瘤活性。

研究人员证明ZIKV以SOX2依赖性方式优先感染和杀死了髓母细胞瘤和室管膜瘤中的GSC和干细胞样细胞。与AXL相比，靶向SOX2可以大大减轻ZIKV感染。作为SOX2介导的ZIKV感染的机制，研究人员确定了抗病毒干扰素应答基因（ISG）的反向表达以及与整合素αv（ITGAV）的正相关。ZIKV感染被ITGAV或其结合伴侣ITGB5的遗传靶向以及整合素αvβ5的特异性抗体所破坏。ZIKV在人类成熟脑类器官体和GBM手术标本中选择性清除了GSC，而整合素αvβ5抑制逆转了这一效果。总的来说，这项研究确定整合素αvβ5是对GBM维持和ZIKV感染必不可少的功能性癌症干细胞标记，提供了潜在的脑肿瘤治疗方法。

附：英文原文

Title: Zika Virus Targets Glioblastoma Stem Cells through a SOX2-Integrin αvβ5 Axis

Author: Zhe Zhu, Pinar Mesci, Jean A. Bernatchez, Ryan C. Gimple, Xiuxing Wang, Simon T. Schafer, Hiromi I. Wettersten, Sungjun Beck, Alex E. Clark, Qiulian Wu, Briana C. Prager, Leo J.Y. Kim, Rekha Dhanwani, Sonia Sharma, Alexandra Garancher, Sara M. Weis, Stephen C. Mack, Priscilla D. Negraes, Cleber A. Trujillo, Luiz O. Penalva, Jing Feng, Zhou Lan, Rong Zhang, Alex W. Wessel, Sanjay Dhawan, Michael S. Diamond, Clark C. Chen, Robert J. Wechsler-Reya, Fred H. Gage, Hongzhen Hu, Jair L. Siqueira-Neto, Alysson R. Muotri, David A. Cheresh, Jeremy N. Rich

Issue&Volume: January 16, 2020

Abstract: Zika virus (ZIKV) causes microcephaly by killing neural precursor cells (NPCs) andother brain cells. ZIKV also displays therapeutic oncolytic activity against glioblastoma(GBM) stem cells (GSCs). Here we demonstrate that ZIKV preferentially infected andkilled GSCs and stem-like cells in medulloblastoma and ependymoma in a SOX2-dependentmanner. Targeting SOX2 severely attenuated ZIKV infection, in contrast to AXL. Asmechanisms of SOX2-mediated ZIKV infection, we identified inverse expression of antiviralinterferon response genes (ISGs) and positive correlation with integrin αv (ITGAV). ZIKV infection was disrupted by genetic targeting of ITGAV or its bindingpartner ITGB5 and by an antibody specific for integrin αvβ5. ZIKV selectively eliminated GSCs from species-matched human mature cerebral organoidsand GBM surgical specimens, which was reversed by integrin αvβ5 inhibition. Collectively, our studies identify integrin αvβ5 as a functional cancer stem cell marker essential for GBM maintenance and ZIKV infection,providing potential brain tumor therapy.

DOI: 10.1016/j.stem.2019.11.016

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30471-0

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