A surrogate animal model for screening of ebola and marburg glycoprotein-targeting drugs using pseudotyped vesicular stomatitis viruses

Takeshi Saito, Junki Maruyama, Noriyo Nagata, Mao Isono, Kosuke Okuya, Yoshihiro Takadate, Yurie Kida, Hiroko Miyamoto, Akina Mori-Kajihara, Takanari Hattori, Wakako Furuyama, Shinya Ogawa, Shigeru Iida, Ayato Takada

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number923
JournalViruses
Volume12
Issue number9
DOIs
StatePublished - Sep 2020

Keywords

  • Animal model
  • Drug screening
  • Ebola virus
  • Filovirus
  • Marburg virus
  • Recombinant vesicular stomatitis virus
  • Syrian hamster

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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  • Cite this

    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