Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development

At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was detected in Wuhan, China, that spread rapidly around the world, with severe consequences for human health and the global economy. Here, we assessed the replicative ability and pathogenesis of SA...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 117; no. 28; pp. 16587 - 16595
Main Authors Imai, Masaki, Iwatsuki-Horimoto, Kiyoko, Hatta, Masato, Loeber, Samantha, Halfmann, Peter J., Nakajima, Noriko, Watanabe, Tokiko, Ujie, Michiko, Takahashi, Kenta, Ito, Mutsumi, Yamada, Shinya, Fan, Shufang, Chiba, Shiho, Kuroda, Makoto, Guan, Lizheng, Takada, Kosuke, Armbrust, Tammy, Balogh, Aaron, Furusawa, Yuri, Okuda, Moe, Ueki, Hiroshi, Yasuhara, Atsuhiro, Sakai-Tagawa, Yuko, Lopes, Tiago J. S., Kiso, Maki, Yamayoshi, Seiya, Kinoshita, Noriko, Ohmagari, Norio, Hattori, Shin-ichiro, Takeda, Makoto, Mitsuya, Hiroaki, Krammer, Florian, Suzuki, Tadaki, Kawaoka, Yoshihiro
Format Journal Article
LanguageEnglish
Published Washington National Academy of Sciences 14.07.2020
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Summary:At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was detected in Wuhan, China, that spread rapidly around the world, with severe consequences for human health and the global economy. Here, we assessed the replicative ability and pathogenesis of SARS-CoV-2 isolates in Syrian hamsters. SARS-CoV-2 isolates replicated efficiently in the lungs of hamsters, causing severe pathological lung lesions following intranasal infection. In addition, microcomputed tomographic imaging revealed severe lung injury that shared characteristics with SARS-CoV-2−infected human lung, including severe, bilateral, peripherally distributed, multilobular ground glass opacity, and regions of lung consolidation. SARS-CoV-2−infected hamsters mounted neutralizing antibody responses and were protected against subsequent rechallenge with SARS-CoV-2. Moreover, passive transfer of convalescent serum to naïve hamsters efficiently suppressed the replication of the virus in the lungs even when the serum was administrated 2 d postinfection of the serum-treated hamsters. Collectively, these findings demonstrate that this Syrian hamster model will be useful for understanding SARS-CoV-2 pathogenesis and testing vaccines and antiviral drugs.
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1M. Imai, K.I.-H., M.H., S.L., P.J.H., and N.N. contributed equally to this work.
Author contributions: M. Imai, K.I.-H., M.H., S.L., P.J.H., N.N., and Y.K. designed research; M. Imai, K.I.-H., M.H., P.J.H., T.W., M.U., M. Ito, S. Yamada, S.F., S.C., M. Kuroda, L.G., K. Takada, T.A., A.B., Y.F., M.O., H.U., A.Y., Y.S.-T., M. Kiso, and S. Yamayoshi performed research; N.K., N.O., S.-i.H., M.T., H.M., and F.K. contributed new reagents/analytic tools; M. Imai, K.I.-H., M.H., S.L., P.J.H., N.N., K. Takahashi, T.J.S.L., T.S., and Y.K. analyzed data; M. Imai, K.I.-H., M.H., S.L., P.J.H., N.N., and Y.K. wrote the paper; N.K., N.O., S.-i.H., and H.M. provided the clinical samples; M.T. provided the VeroE6/TMPRSS2 cells; and F.K. provided the plasmid encoding the receptor-binding domain (RBD) of SARS-CoV-2.
Edited by Robert L. Coffman, University of California, Santa Cruz, CA, and approved June 12, 2020 (received for review May 15, 2020)
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.2009799117