Molecules and Cells

  • 제45권12호
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  • Pages.896-910
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  • 2022
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Temporal Transcriptome Analysis of SARS-CoV-2-Infected Lung and Spleen in Human ACE2-Transgenic Mice

  • Jung Ah, Kim (Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Sung-Hee, Kim (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Jung Seon, Seo (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Hyuna, Noh (Korea Mouse Phenotyping Center, Seoul National University) ;
  • Haengdueng, Jeong (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Jiseon, Kim (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Donghun, Jeon (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Jeong Jin, Kim (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Dain, On (Korea Mouse Phenotyping Center, Seoul National University) ;
  • Suhyeon, Yoon (Korea Mouse Phenotyping Center, Seoul National University) ;
  • Sang Gyu, Lee (Interdisciplinary Program for Bioinformatics, Seoul National University) ;
  • Youn Woo, Lee (Department of Nuclear Medicine, Seoul National University Bundang Hospital) ;
  • Hui Jeong, Jang (Department of Nuclear Medicine, Seoul National University Bundang Hospital) ;
  • In Ho, Park (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Jooyeon, Oh (Department of Microbiology, Yonsei University College of Medicine) ;
  • Sang-Hyuk, Seok (Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University) ;
  • Yu Jin, Lee (Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University) ;
  • Seung-Min, Hong (Laboratory of Avian Diseases, BK21 PLUS Program for Veterinary Science and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University) ;
  • Se-Hee, An (Laboratory of Avian Diseases, BK21 PLUS Program for Veterinary Science and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University) ;
  • Joon-Yong, Bae (Department of Microbiology, Institute for Viral Diseases, Biosafety Center, Korea University College of Medicine) ;
  • Jung-ah, Choi (Science Unit, International Vaccine Institute) ;
  • Seo Yeon, Kim (Preclinical Research Center, Seoul National University Bundang Hospital) ;
  • Young Been, Kim (Preclinical Research Center, Seoul National University Bundang Hospital) ;
  • Ji-Yeon, Hwang (Preclinical Research Center, Seoul National University Bundang Hospital) ;
  • Hyo-Jung, Lee (Department of Periodontology, Section of Dentistry, Seoul National University Bundang Hospital) ;
  • Hong Bin, Kim (Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Dae Gwin, Jeong (Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Daesub, Song (Department of Veterinary Medicine Virology Laboratory, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University) ;
  • Manki, Song (Science Unit, International Vaccine Institute) ;
  • Man-Seong, Park (Department of Microbiology, Institute for Viral Diseases, Biosafety Center, Korea University College of Medicine) ;
  • Kang-Seuk, Choi (Laboratory of Avian Diseases, BK21 PLUS Program for Veterinary Science and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University) ;
  • Jun Won, Park (Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University) ;
  • Jun-Won, Yun (Laboratory of Veterinary Toxicology, College of Veterinary Medicine, Seoul National University) ;
  • Jeon-Soo, Shin (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Ho-Young, Lee (Department of Nuclear Medicine, Seoul National University Bundang Hospital) ;
  • Jun-Young, Seo (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Ki Taek, Nam (Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Heon Yung, Gee (Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Je Kyung, Seong (Korea Mouse Phenotyping Center, Seoul National University)
  • 투고 : 2022.06.02
  • 심사 : 2022.08.05
  • 발행 : 2022.12.31
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초록

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.

키워드

과제정보

This study was supported by the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT) (2020M3A9D5A01082439 and 2018R1A5A2025079, to H.Y.G., 2016M3A9D5A01952416 to K.T.N., and Bio & Medical Technology Development Program 2021M3H9A1038083 to K.T.N.).

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