Development and characterization of a guinea pig model for Marburg virus

The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can...

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Bibliographic Details
Published in:Dōngwùxué yánjiū 2018-01, Vol.39 (1), p.32-41
Main Authors: Wong, Gary, Cao, Wen-Guang, He, Shi-Hua, Zhang, Zi-Rui, Zhu, Wen-Jun, Moffat, Estella, Ebihara, Hideki, Embury-Hyatt, Carissa, Qiu, Xiang-Guo
Format: Article
Language:English
Subjects:
Adaptation
Animal models
Body organs
Fatalities
Genomes
Guinea pigs
Infections
Infectious diseases
Kidneys
Lethality
Liver
Lungs
Lymphopenia
Marburg disease
Marburgvirus
Mice
Microbiological strains
Mortality causes
Mutation
Organs
Rodents
Spleen
Swine
Symptoms
Thrombocytopenia
Tissue
Tissue culture
Toxicity tests
Viral diseases
Viremia
Viruses
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Summary:The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA), with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP) model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs (MARV/AngGA). Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7-9 days after infection, and the LD50 was calculated to be 1.1 x10-1 TCID50 (median tissue culture infective dose). Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.
ISSN:0254-5853
DOI:10.24272/j.issn.2095-8137.2017.054