Laboratory for Translational and Molecular Imaging, Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore, Singapore, 169857.
Laboratory of Human Neural Models, Neuroscience and Behavioural Disorders Programme, Duke-NUS Medical School, Singapore, Singapore, 169857.
J Transl Med. 2024 Feb 2;22(1):126. doi: 10.1186/s12967-024-04930-4.
Glioblastoma multiforme (GBM) is the most common malignant primary brain cancer affecting the adult population. Median overall survival for GBM patients is poor (15 months), primarily due to high rates of tumour recurrence and the paucity of treatment options. Oncolytic virotherapy is a promising treatment alternative for GBM patients, where engineered viruses selectively infect and eradicate cancer cells by inducing cell lysis and eliciting robust anti-tumour immune response. In this study, we evaluated the oncolytic potency of live-attenuated vaccine strains of Zika virus (ZIKV-LAV) against human GBM cells in vitro. Our findings revealed that Axl and integrin αβ function as cellular receptors mediating ZIKV-LAV infection in GBM cells. ZIKV-LAV strains productively infected and lysed human GBM cells but not primary endothelia and terminally differentiated neurons. Upon infection, ZIKV-LAV mediated GBM cell death via apoptosis and pyroptosis. This is the first in-depth molecular dissection of how oncolytic ZIKV infects and induces death in tumour cells.
多形性胶质母细胞瘤（GBM）是最常见的影响成年人群体的恶性原发性脑癌。GBM 患者的总体中位生存期较差（15 个月），主要是由于肿瘤复发率高和治疗选择有限。溶瘤病毒治疗是 GBM 患者的一种有前途的治疗选择，其中经过工程改造的病毒通过诱导细胞裂解和引发强烈的抗肿瘤免疫反应，选择性感染和消灭癌细胞。在这项研究中，我们评估了活减毒的寨卡病毒（ZIKV-LAV）疫苗株对体外培养的人类 GBM 细胞的溶瘤效力。我们的研究结果表明，Axl 和整合素αβ作为细胞受体，介导 ZIKV-LAV 在 GBM 细胞中的感染。ZIKV-LAV 株可有效感染和裂解人类 GBM 细胞，但不能感染原代内皮细胞和终末分化神经元。感染后，ZIKV-LAV 通过细胞凋亡和细胞焦亡介导 GBM 细胞死亡。这是首次深入剖析溶瘤寨卡病毒如何感染和诱导肿瘤细胞死亡。
