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

Virologica Sinica 2024年第3期39卷 434-446页

作者： Wanying Yang Wujian Li Wujie Zhou Shen Wang Weiqi Wang Zhenshan Wang Na Feng Tiecheng Wang Ying Xie Yongkun Zhao Feihu Yan Xianzhu Xia Hebei Key Lab of Laboratory Animal Science Department of Laboratory Animal ScienceHebei Medical UniversityShijiazhuang050017China Key Laboratory of Jilin Province for Zoonosis Prevention and Control Changchun Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchun130122China College of Veterinary Medicine Jilin UniversityChangchun130062China College of Veterinary Medicine Jilin Agricultural UniversityChangchun130118China

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 ***,accessible and convenient animal models are urgently needed to promote prophylactic and therapeutic approaches against *** 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 *** 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 *** 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 ***,equine anti-EBOV immunoglobulins and a subunit vaccine were validated using this ***,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.

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

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