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Zoological Research    2018, Vol. 39 Issue (1) : 32-41     DOI: 10.24272/j.issn.2095-8137.2017.054
Articles |
Development and characterization of a guinea pig model for Marburg virus
Gary Wong1,2,3,4, Wen-Guang Cao1,4, Shi-Hua He1, Zi-Rui Zhang1,4, Wen-Jun Zhu1,4, Estella Moffat5, Hideki Ebihara6, Carissa Embury-Hyatt5, Xiang-Guo Qiu1,4,*
1 Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada
2 Shenzhen Key Laboratory of Pathogen and Immunity, State Key Discipline of Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen Guangzhou 518020, China
3 Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
4 Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada
5 National Center for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg R3E 3M4, Canada
6 Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
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Abstract  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/Ang-GA). 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 1.1×10–1 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.
Keywords Marburg virus      Guinea pig      Animal model      Pathogenesis      Host adaptation     
Fund:This study was supported by the Public Health Agency of Canada (PHAC), partially supported by the NIH and CIHR grants to X. G. Qiu (U19 AI109762-1 and CIHR-IER-143487, respectively), and grants from the National Natural Science Foundation of China International Cooperation and Exchange Program (8161101193) and National Science and Technology Major Project (2016ZX10004222) to G. Wong
Corresponding Authors: Xiang-Guo Qiu,   
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Gary Wong, Wen-Guang Cao, Shi-Hua He, Zi-Rui Zhang, Wen-Jun Zhu, Estella Moffat, Hideki Ebihara, Carissa Embury-Hyatt, Xiang-Guo Qiu. Development and characterization of a guinea pig model for Marburg virus. Zoological Research, 10.24272/j.issn.2095-8137.2017.054
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