Department of Virology, LG Schreiber, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.
Department of Neurosurgery, Asklepios Kliniken Hamburg GmbH, Asklepios Klinik Nord, Standort Heidberg, 22417 Hamburg, Germany.
Int J Mol Sci. 2023 Sep 23;24(19):14487. doi: 10.3390/ijms241914487.
A fundamental idea for targeting glioblastoma cells is to exploit the neurotropic properties of Zika virus (ZIKV) through its two outer envelope proteins, prM and E. This study aimed to develop envelope glycoproteins for pseudotyping retroviral vectors that can be used for efficient tumor cell infection. Firstly, the retroviral vector pNLAM was packaged using wild-type ZIKV E to generate an E-HIV pseudotype. E-HIV infection rates for tumor cells were higher than those of normal prME pseudotyped particles and the traditionally used vesicular stomatitis virus G (VSV-G) pseudotypes, indicating that protein E alone was sufficient for the formation of infectious pseudotyped particles. Secondly, two envelope chimeras, E41.1 and E41.2, with the E wild-type transmembrane domain replaced by the gp41 transmembrane and cytoplasmic domains, were constructed; pNLAM or pNLAM packaged with E41.1 or E41.2 constructs showed infectivity for tumor cells, with the highest rates observed for E41.2. This envelope construct can be used not only as a tool to further develop oncolytic pseudotyped viruses for therapy, but also as a new research tool to study changes in tumor cells after the transfer of genes that might have therapeutic potential.
靶向神经胶质瘤细胞的一个基本思路是利用寨卡病毒（ZIKV）的两个外膜蛋白，prM 和 E，发挥其神经营养特性。本研究旨在开发包膜糖蛋白，对逆转录病毒载体进行假型化处理，从而可以有效地感染肿瘤细胞。首先，使用野生型 ZIKV E 对逆转录病毒载体 pNLAM 进行包装，生成 E-HIV 假型。与正常 prME 假型颗粒和传统使用的水疱性口炎病毒 G（VSV-G）假型相比，E-HIV 对肿瘤细胞的感染率更高，表明仅 E 蛋白本身就足以形成感染性假型颗粒。其次，构建了两种包膜嵌合体，E41.1 和 E41.2，用 gp41 跨膜和胞质结构域替换了 E 野生型跨膜结构域；pNLAM 或用 E41.1 或 E41.2 构建体包装的 pNLAM 显示对肿瘤细胞具有感染性，E41.2 的感染率最高。这种包膜构建体不仅可以用作进一步开发溶瘤性假型病毒进行治疗的工具，也可以用作研究转染具有潜在治疗作用的基因后肿瘤细胞变化的新研究工具。
