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Volume 12
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10.3390/v12090923
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Article

A Surrogate Animal Model for Screening of Ebola and Marburg Glycoprotein-Targeting Drugs Using Pseudotyped Vesicular Stomatitis Viruses

by
Takeshi Saito
1,
Junki Maruyama
2,
Noriyo Nagata
3,
Mao Isono
1,
Kosuke Okuya
1,
Yoshihiro Takadate
1,
Yurie Kida
1,
Hiroko Miyamoto
1,
Akina Mori-Kajihara
1,
Takanari Hattori
1,
Wakako Furuyama
4,
Shinya Ogawa
5,
Shigeru Iida
5 and
Ayato Takada
1,6,*
1
Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan
2
Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA
3
Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan
4
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, USA
5
Tokyo Research Park, Kyowa Kirin Co., Ltd., Tokyo 194-0023, Japan
6
Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo 001-0020, Japan
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(9), 923; https://doi.org/10.3390/v12090923
Submission received: 21 July 2020 / Revised: 20 August 2020 / Accepted: 20 August 2020 / Published: 22 August 2020
(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)
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Abstract

Filoviruses, including Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic fever in humans and nonhuman primates with high mortality rates. There is no approved therapy against these deadly viruses. Antiviral drug development has been hampered by the requirement of a biosafety level (BSL)-4 facility to handle infectious EBOV and MARV because of their high pathogenicity to humans. In this study, we aimed to establish a surrogate animal model that can be used for anti-EBOV and -MARV drug screening under BSL-2 conditions by focusing on the replication-competent recombinant vesicular stomatitis virus (rVSV) pseudotyped with the envelope glycoprotein (GP) of EBOV (rVSV/EBOV) and MARV (rVSV/MARV), which has been investigated as vaccine candidates and thus widely used in BSL-2 laboratories. We first inoculated mice, rats, and hamsters intraperitoneally with rVSV/EBOV and found that only hamsters showed disease signs and succumbed within 4 days post-infection. Infection with rVSV/MARV also caused lethal infection in hamsters. Both rVSV/EBOV and rVSV/MARV were detected at high titers in multiple organs including the liver, spleen, kidney, and lungs of infected hamsters, indicating acute and systemic infection resulting in fatal outcomes. Therapeutic effects of passive immunization with an anti-EBOV neutralizing antibody were specifically observed in rVSV/EBOV-infected hamsters. Thus, this animal model is expected to be a useful tool to facilitate in vivo screening of anti-filovirus drugs targeting the GP molecule.
Keywords: Filovirus; Ebola virus; Marburg virus; recombinant vesicular stomatitis virus; Syrian hamster; animal model; drug screening Filovirus; Ebola virus; Marburg virus; recombinant vesicular stomatitis virus; Syrian hamster; animal model; drug screening

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MDPI and ACS Style

Saito, T.; Maruyama, J.; Nagata, N.; Isono, M.; Okuya, K.; Takadate, Y.; Kida, Y.; Miyamoto, H.; Mori-Kajihara, A.; Hattori, T.; et al. A Surrogate Animal Model for Screening of Ebola and Marburg Glycoprotein-Targeting Drugs Using Pseudotyped Vesicular Stomatitis Viruses. Viruses 2020, 12, 923. https://doi.org/10.3390/v12090923

AMA Style

Saito T, Maruyama J, Nagata N, Isono M, Okuya K, Takadate Y, Kida Y, Miyamoto H, Mori-Kajihara A, Hattori T, et al. A Surrogate Animal Model for Screening of Ebola and Marburg Glycoprotein-Targeting Drugs Using Pseudotyped Vesicular Stomatitis Viruses. Viruses. 2020; 12(9):923. https://doi.org/10.3390/v12090923

Chicago/Turabian Style

Saito, Takeshi, Junki Maruyama, Noriyo Nagata, Mao Isono, Kosuke Okuya, Yoshihiro Takadate, Yurie Kida, Hiroko Miyamoto, Akina Mori-Kajihara, Takanari Hattori, and et al. 2020. "A Surrogate Animal Model for Screening of Ebola and Marburg Glycoprotein-Targeting Drugs Using Pseudotyped Vesicular Stomatitis Viruses" Viruses 12, no. 9: 923. https://doi.org/10.3390/v12090923

APA Style

Saito, T., Maruyama, J., Nagata, N., Isono, M., Okuya, K., Takadate, Y., Kida, Y., Miyamoto, H., Mori-Kajihara, A., Hattori, T., Furuyama, W., Ogawa, S., Iida, S., & Takada, A. (2020). A Surrogate Animal Model for Screening of Ebola and Marburg Glycoprotein-Targeting Drugs Using Pseudotyped Vesicular Stomatitis Viruses. Viruses, 12(9), 923. https://doi.org/10.3390/v12090923

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