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

Authors :
Yang W
Li W
Zhou W
Wang S
Wang W
Wang Z
Feng N
Wang T
Xie Y
Zhao Y
Yan F
Xia X
Source :
Virologica Sinica [Virol Sin] 2024 Jun; Vol. 39 (3), pp. 434-446. Date of Electronic Publication: 2024 Mar 29.
Publication Year :
2024

Abstract

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.<br />Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.<br /> (Copyright © 2024 The Authors. Publishing services by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1995-820X
Volume :
39
Issue :
3
Database :
MEDLINE
Journal :
Virologica Sinica
Publication Type :
Academic Journal
Accession number :
38556051
Full Text :
https://doi.org/10.1016/j.virs.2024.03.010