He Wenwen, Cui Huan, Wang Shen, Liang Bo, Zhang Cheng, Wang Weiqi, Wang Qi, Li Wujian, Zhao Yongkun, Wang Tiecheng, Liu Zhuoran, Liu Bin, Yan Feihu, Yang Songtao, Xia Xianzhu
Department of Laboratory Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China.
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China.
Microorganisms. 2023 Feb 8;11(2):431. doi: 10.3390/microorganisms11020431.
The frequent emergence of SARS-CoV-2 variants thwarts the prophylactic and therapeutic countermeasures confronting COVID-19. Among them, the Delta variant attracts widespread attention due to its high pathogenicity and fatality rate compared with other variants. However, with the emergence of new variants, studies on Delta variants have been gradually weakened and ignored. In this study, a replication-competent recombinant virus carrying the S protein of the SARS-CoV-2 Delta variant was established based on the vesicular stomatitis virus (VSV), which presented a safe alternative model for studying the Delta variant. The recombinant virus showed a replication advantage in Vero E6 cells, and the viral titers reach 10 TCID/mL at 36 h post-inoculation. In the VSV-vectored recombinant platform, the spike proteins of the Delta variant mediated higher fusion activity and syncytium formation than the wild-type strain. Notably, the recombinant virus was avirulent in BALB/c mice, Syrian hamsters, 3-day ICR suckling mice, and IFNAR/GR mice. It induced protective neutralizing antibodies in rodents, and protected the Syrian hamsters against the SARS-CoV-2 Delta variant infection. Meanwhile, the eGFP reporter of recombinant virus enabled the visual assay of neutralizing antibodies. Therefore, the recombinant virus could be a safe and convenient surrogate tool for authentic SARS-CoV-2. This efficient and reliable model has significant potential for research on viral-host interactions, epidemiological investigation of serum-neutralizing antibodies, and vaccine development.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的频繁出现阻碍了针对2019冠状病毒病（COVID-19）的预防和治疗措施。其中，德尔塔变体因其与其他变体相比具有较高的致病性和致死率而备受关注。然而，随着新变体的出现，对德尔塔变体的研究逐渐被削弱和忽视。在本研究中，基于水泡性口炎病毒（VSV）构建了一种携带SARS-CoV-2德尔塔变体S蛋白的具有复制能力的重组病毒，为研究德尔塔变体提供了一种安全的替代模型。该重组病毒在Vero E6细胞中显示出复制优势，接种后36小时病毒滴度达到10 TCID/mL。在VSV载体重组平台中，德尔塔变体的刺突蛋白介导的融合活性和多核体形成高于野生型毒株。值得注意的是，该重组病毒对BALB/c小鼠、叙利亚仓鼠、3日龄ICR乳鼠和IFNAR/GR小鼠无毒。它在啮齿动物中诱导产生保护性中和抗体，并保护叙利亚仓鼠免受SARS-CoV-2德尔塔变体感染。同时，重组病毒的eGFP报告基因能够对中和抗体进行可视化检测。因此，该重组病毒可能是真实SARS-CoV-2的一种安全便捷的替代工具。这种高效可靠的模型在病毒-宿主相互作用研究、血清中和抗体的流行病学调查以及疫苗开发方面具有巨大潜力。
