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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
A surrogate animal model for screening of ebola and marburg glycoprotein-targeting drugs using pseudotyped vesicular stomatitis viruses
Viruses, Volume 12, No. 9, Article 923, Year 2020
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Description
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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Authors & Co-Authors
Saito, Takeshi
Japan, Sapporo
Hokkaido University
Maruyama, Junki
United States, Galveston
The University of Texas Medical Branch at Galveston
Nagata, Noriyos
Japan, Tokyo
National Institute of Infectious Diseases
Isono, Mao
Japan, Sapporo
Hokkaido University
Okuya, Kosuke
Japan, Sapporo
Hokkaido University
Takadate, Yoshihiro
Japan, Sapporo
Hokkaido University
Kida, Yurie
Japan, Sapporo
Hokkaido University
Miyamoto, Hiroko
Japan, Sapporo
Hokkaido University
Mori-Kajihara, Akina
Japan, Sapporo
Hokkaido University
Hattori, Takanari
Japan, Sapporo
Hokkaido University
Furuyama, Wakako
United States, Bethesda
National Institutes of Health Nih
Takada, Ayato
Japan, Sapporo
Hokkaido University
Statistics
Citations: 6
Authors: 12
Affiliations: 5
Identifiers
Doi:
10.3390/v12090923
ISSN:
19994915
Research Areas
Health System And Policy
Infectious Diseases
Maternal And Child Health