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Apr, 2024;24 (2): e7.

Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice.

Jung Ah Kim, Sung-Hee Kim, Jeong Jin Kim, Hyuna Noh, Su-Bin Lee, Haengdueng Jeong, Jiseon Kim, Donghun Jeon, Jung Seon Seo, Dain On, Suhyeon Yoon, Sang Gyu Lee, Youn Woo Lee, Hui Jeong Jang, In Ho Park, Jooyeon Oh, Sang-Hyuk Seok, Yu Jin Lee, Seung-Min Hong, Se-Hee An, Joon-Yong Bae, Jung-Ah Choi, Seo Yeon Kim, Young Been Kim, Ji-Yeon Hwang, Hyo-Jung Lee, Hong Bin Kim, Dae Gwin Jeong, Daesub Song, Manki Song, Man-Seong Park, Kang-Seuk Choi, Jun Won Park, Jun-Won Yun, Jeon-Soo Shin, Ho-Young Lee, Ho-Keun Kwon, Jun-Young Seo, Ki Taek Nam, Heon Yung Gee, Je Kyung Seong
Author Information
  1. Jung Ah Kim: Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  2. Sung-Hee Kim: Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  3. Jeong Jin Kim: Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  4. Hyuna Noh: Korea Mouse Phenotyping Center, Seoul National University, Seoul 08826, Korea. ORCID
  5. Su-Bin Lee: Department of Microbiology and Immunology and Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  6. Haengdueng Jeong: Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  7. Jiseon Kim: Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  8. Donghun Jeon: Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  9. Jung Seon Seo: Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  10. Dain On: Korea Mouse Phenotyping Center, Seoul National University, Seoul 08826, Korea. ORCID
  11. Suhyeon Yoon: Korea Mouse Phenotyping Center, Seoul National University, Seoul 08826, Korea. ORCID
  12. Sang Gyu Lee: Interdisciplinary Program for Bioinformatics, Seoul National University, Seoul 08826, Korea. ORCID
  13. Youn Woo Lee: Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam 23488, Korea. ORCID
  14. Hui Jeong Jang: Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam 23488, Korea. ORCID
  15. In Ho Park: Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  16. Jooyeon Oh: Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  17. Sang-Hyuk Seok: Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24342, Korea. ORCID
  18. Yu Jin Lee: Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24342, Korea. ORCID
  19. 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, Seoul 08826, Korea. ORCID
  20. 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, Seoul 08826, Korea. ORCID
  21. Joon-Yong Bae: Department of Microbiology, Institute for Viral Diseases, Biosafety Center, Korea University College of Medicine, Seoul 02842, Korea. ORCID
  22. Jung-Ah Choi: Science Unit, International Vaccine Institute, Seoul 08826, Korea. ORCID
  23. Seo Yeon Kim: Preclinical Research Center, Seoul National University Bundang Hospital, Seongnam 23488, Korea. ORCID
  24. Young Been Kim: Preclinical Research Center, Seoul National University Bundang Hospital, Seongnam 23488, Korea. ORCID
  25. Ji-Yeon Hwang: Preclinical Research Center, Seoul National University Bundang Hospital, Seongnam 23488, Korea. ORCID
  26. Hyo-Jung Lee: Department of Periodontology, Section of Dentistry, Seoul National University Bundang Hospital, Seongnam 23620, Korea. ORCID
  27. Hong Bin Kim: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 23620, Korea. ORCID
  28. Dae Gwin Jeong: Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34242, Korea. ORCID
  29. Daesub Song: Department of Veterinary Medicine Virology Laboratory, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea. ORCID
  30. Manki Song: Science Unit, International Vaccine Institute, Seoul 08826, Korea. ORCID
  31. Man-Seong Park: Department of Microbiology, Institute for Viral Diseases, Biosafety Center, Korea University College of Medicine, Seoul 02842, Korea. ORCID
  32. 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, Seoul 08826, Korea. ORCID
  33. Jun Won Park: Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24342, Korea. ORCID
  34. Jun-Won Yun: Laboratory of Veterinary Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea. ORCID
  35. Jeon-Soo Shin: Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  36. Ho-Young Lee: Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam 23488, Korea. ORCID
  37. Ho-Keun Kwon: Department of Microbiology and Immunology and Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  38. Jun-Young Seo: Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  39. Ki Taek Nam: Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  40. Heon Yung Gee: Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea. ORCID
  41. Je Kyung Seong: Korea Mouse Phenotyping Center, Seoul National University, Seoul 08826, Korea. ORCID
PMID: 38725670 DOI: 10.4110/in.2024.24.e7

Abstract

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×10 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×10 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×10 PFU-virus-infected lungs from 2 dpi, but not in 1×10 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×10 PFU; however, 1×10 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Keywords

Dose-response relationship, immunologic Immune response K18-hACE2 mice SARS-CoV-2 Transcriptome profiling

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Journal Article

Word Cloud

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