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Establishment and application of a surrogate model for human Ebola virus disease in BSL-2 laboratory.
- 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.)
- Subjects :
- Animals
Female
Humans
Vesiculovirus genetics
Vesiculovirus pathogenicity
Antibodies, Viral blood
Cricetinae
Viral Load
Glycoproteins genetics
Glycoproteins immunology
Hemorrhagic Fever, Ebola virology
Hemorrhagic Fever, Ebola pathology
Disease Models, Animal
Ebolavirus genetics
Ebolavirus pathogenicity
Mesocricetus
Subjects
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