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

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Title: A Surrogate Animal Model for Screening of Ebola and Marburg Glycoprotein-Targeting Drugs Using Pseudotyped Vesicular Stomatitis Viruses
Authors: Saito, Takeshi Browse this author
Maruyama, Junki Browse this author
Nagata, Noriyo Browse this author
Isono, Mao Browse this author
Okuya, Kosuke Browse this author
Takadate, Yoshihiro Browse this author
Kida, Yurie Browse this author
Miyamoto, Hiroko Browse this author
Mori-Kajihara, Akina Browse this author
Hattori, Takanari Browse this author
Furuyama, Wakako Browse this author
Ogawa, Shinya Browse this author
Iida, Shigeru Browse this author
Takada, Ayato Browse this author
Keywords: Filovirus
Ebola virus
Marburg virus
recombinant vesicular stomatitis virus
Syrian hamster
animal model
drug screening
Issue Date: Sep-2020
Publisher: MDPI
Journal Title: Viruses-Basel
Volume: 12
Issue: 9
Start Page: 923
Publisher DOI: 10.3390/v12090923
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.
Type: article
Appears in Collections:国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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