Immune Netw.
2024 Apr;24(2):e7. 10.4110/in.2024.24.e7.
Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice
- Kim JA
1 - Kim SH2
- Kim JJ2
- Noh H3
- Lee Sb4
- Jeong H2
- Kim J2
- Jeon D2
- Seo JS2
- On D3,5
- Yoon S3
- Lee SG6
- Lee YW7
- Jang HJ7
- Park IH2,8
- Oh J9
- Seok SH10
- Lee YJ10
- Hong SM11
- An SH11
- Bae JY12
- Choi Ja13
- Kim SY14
- Kim YB14
- Hwang JY14
- Lee HJ15
- Kim HB16
- Jeong DG17
- Song D18
- Song M13
- Park MS12
- Choi KS11
- Park JW10
- Yun JW19
- Shin JS2,8,9
- Lee HY7,20
- Kwon HK4
- Seo JY2
- Nam KT2
- Gee HY1
- Seong JK3,5,6,21
- Affiliations
-
- 1Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea
- 2Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea
- 3Korea Mouse Phenotyping Center, Seoul National University, Seoul 08826, Korea
- 4Department of Microbiology and Immunology and Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Korea
- 5Laboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
- 6Interdisciplinary Program for Bioinformatics, Seoul National University, Seoul 08826, Korea
- 7Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam 23488, Korea
- 8Institute of Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Korea
- 9Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, Korea
- 10Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24342, Korea
- 11Laboratory 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
- 12Department of Microbiology, Institute for Viral Diseases, Biosafety Center, Korea University College of Medicine, Seoul 02842, Korea
- 13Science Unit, International Vaccine Institute, Seoul 08826, Korea
- 14Preclinical Research Center, Seoul National University Bundang Hospital, Seongnam 23488, Korea
- 15Department of Periodontology, Section of Dentistry, Seoul National University Bundang Hospital, Seongnam 23620, Korea
- 16Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 23620, Korea
- 17Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34242, Korea
- 18Department of Veterinary Medicine Virology Laboratory, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea
- 19Laboratory of Veterinary Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
- 20Department of Nuclear Medicine, Seoul National University, College of Medicine, Seoul 03080, Korea
- 21BIO-MAX Institute, Seoul National University, Seoul 08826, Korea
- KMID: 2557928
- DOI: http://doi.org/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, 1×105 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 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105 PFU; however, 1×102 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.
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