Establishment and application of a surrogate model for human Ebola virus disease in BSL-2 laboratory

文献类型： 外文期刊

第一作者： Yang, Wanying

作者： Yang, Wanying;Xie, Ying;Yang, Wanying;Li, Wujian;Zhou, Wujie;Wang, Shen;Wang, Weiqi;Wang, Zhenshan;Feng, Na;Wang, Tiecheng;Zhao, Yongkun;Yan, Feihu;Xia, Xianzhu;Li, Wujian;Wang, Weiqi;Wang, Zhenshan

作者机构：

关键词： Ebola virus (EBOV); Recombinant vesicular stomatitis virus; Pathogenicity; Syrian hamster; Surrogate models; Vaccine evaluation and drug screening

期刊名称：VIROLOGICA SINICA （ 影响因子：4.3； 五年影响因子：4.3 ）

ISSN： 1674-0769

年卷期： 2024 年 39 卷 3 期

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收录情况： SCI

摘要： The Ebola virus (EBOV) is a member of the Orthoebolavirus genus, Filoviridae family, which causes severe hemorrhagic diseases in humans and non-human primates (NHPs), with a case fatality rate of up to 90%. The development of countermeasures against EBOV has been hindered by the lack of ideal animal models, as EBOV requires handling in biosafety level (BSL)-4 facilities. Therefore, accessible and convenient animal models are urgently needed to promote prophylactic and therapeutic approaches against EBOV. In this study, a recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein (VSV-EBOV/GP) was constructed and applied as a surrogate virus, establishing a lethal infection in hamsters. Following infection with VSV-EBOV/GP, 3-week-old female Syrian hamsters exhibited disease signs such as weight loss, multi-organ failure, severe uveitis, high viral loads, and developed severe systemic diseases similar to those observed in human EBOV patients. All animals succumbed at 2-3 days post-infection (dpi). Histopathological changes indicated that VSV-EBOV/GP targeted liver cells, suggesting that the tissue tropism of VSV-EBOV/GP was comparable to wild-type EBOV (WT EBOV). Notably, the pathogenicity of the VSV-EBOV/GP was found to be species-specific, age-related, gender-associated, and challenge route-dependent. Subsequently, equine anti-EBOV immunoglobulins and a subunit vaccine were validated using this model. Overall, this surrogate model represents a safe, effective, and economical tool for rapid preclinical evaluation of medical countermeasures against EBOV under BSL-2 conditions, which would accelerate technological advances and breakthroughs in confronting Ebola virus disease.

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