Zell Brady N, Swenson Vaille A, Lu Shao-Chia, Wang Lin, Barry Michael A, Ebihara Hideki, Yamaoka Satoko
Virology and Gene Therapy Program, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA.
Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Viruses. 2025 May 9;17(5):688. doi: 10.3390/v17050688.
Ebola virus (EBOV) causes severe disease outbreaks in humans with high case fatality rates. EBOV requires adaptation to cause lethal disease in mice by acquiring single mutations in both the nucleoprotein (NP) and VP24 genes. As an attempt to model mouse-adapted EBOV (MA-EBOV), we engineered novel pentacistronic minigenomes (5xMG) containing a reporter gene, VP40, and glycoprotein genes as well as the NP and VP24 genes from either EBOV or MA-EBOV. The 5xMGs were constructed and optimized, and the produced transcription- and replication-competent virus-like particles (trVLPs) were demonstrated to infect several cell lines. Introduction of the mouse-adaptation mutations did not significantly impact the replication and transcription of the 5xMG or the relative infectivity of the trVLPs in vitro. This work demonstrates the development of the 5xMG system as a new versatile tool to study EBOV biology.
埃博拉病毒（EBOV）可导致人类严重疾病爆发，病死率很高。EBOV需要通过在核蛋白（NP）和VP24基因中均获得单个突变来适应，从而在小鼠中引发致死性疾病。作为构建适应小鼠的EBOV（MA-EBOV）模型的尝试，我们构建了新型五顺反子微型基因组（5xMG），其包含一个报告基因、VP40、糖蛋白基因以及来自EBOV或MA-EBOV的NP和VP24基因。构建并优化了5xMG，所产生的具有转录和复制能力的病毒样颗粒（trVLP）被证明可感染多种细胞系。引入小鼠适应性突变对5xMG的复制和转录或trVLP在体外的相对感染性没有显著影响。这项工作证明了5xMG系统作为研究EBOV生物学的一种新型通用工具的开发。
