한빛사논문
- 조회209
Gi Uk Jeong1,4,5,7,8, Insu Hwang1,6,7,8, Wooseong Lee1,7,8, Ji Hyun Choi1,7,8, Gun Young Yoon1, Hae Soo Kim1, Jeong-Sun Yang2, Kyung-Chang Kim2, Joo-Yeon Lee2, Seong-Jun Kim1, Young-Chan Kwon1,3 and Kyun-Do Kim1
1Center for Infectious Disease Vaccine and Diagnosis Innovation (CEVI), Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
2Center for Emerging Virus Research, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea.
3Medical Chemistry and Pharmacology, University of Science and Technology (UST), Daejeon, Republic of Korea.
4Present address: Division of Infectious Diseases, Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA.
5Present address: Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
6Present address: Division of Vaccine Development Coordination, Center for Vaccine Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea.
7These authors contributed equally: Gi Uk Jeong, Insu Hwang, Wooseong Lee, Ji Hyun Choi.
8These authors contributed equally: Gi Uk Jeong, Insu Hwang, Wooseong Lee, Ji Hyun Choi.
Corresponding authors
Correspondence to Young-Chan Kwon or Kyun-Do Kim.
Abstract
Mouse models expressing human ACE2 for coronavirus disease 2019 have been frequently used to understand its pathogenesis and develop therapeutic strategies against SARS-CoV-2. Given that human TMPRSS2 supports viral entry, replication, and pathogenesis, we established a double-transgenic mouse model expressing both human ACE2 and TMPRSS2 for SARS-CoV-2 infection. Co-overexpression of both genes increased viral infectivity in vitro and in vivo. Double-transgenic mice showed significant body weight loss, clinical disease symptoms, acute lung injury, lung inflammation, and lethality in response to viral infection, indicating that they were highly susceptible to SARS-CoV-2. Pretreatment with the TMPRSS2 inhibitor, nafamostat, effectively reduced virus-induced weight loss, viral replication, and mortality in the double-transgenic mice. Moreover, the susceptibility and differential pathogenesis of SARS-CoV-2 variants were demonstrated in this animal model. Together, our results demonstrate that double-transgenic mice could provide a highly susceptible mouse model for viral infection to understand SARS-CoV-2 pathogenesis and evaluate antiviral therapeutics against coronavirus disease 2019.
논문정보
- Research article
- 2024년 05월 (BRIC 등록일 2024-05-31)
- 국내(교신)+국외 연구진
- 생명과학 > 감염생물학
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