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Peer-reviewedCC BY 4.0Molecular & Cellular Proteomics : MCP

Temporal Proteomic Characterization of SARS-CoV-2-Infected Mouse Lungs

18 more authors
23 affiliations
  1. 1School of Biological Sciences, Seoul National University, Seoul, Republic of Korea
  2. 2Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, Republic of Korea
  3. 3Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, Republic of Korea
  4. 4Laboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, and BK 21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
  5. 5Department of Molecular and Life Science, Hanyang University, Ansan, Republic of Korea
  6. 6Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea
  7. 7Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
  8. 8Department of Biomedical Sciences, School of Medicine, CHA University, CHA BIO COMPLEX, Gyeonggi-do, Republic of Korea
  9. 9Department of Medical Informatics and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
  10. 10Interdisciplinary Program for Bioinformaics, Seoul National University, Seoul, Republic of Korea
  11. 11Department of Periodontology, Section of Dentistry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
  12. 12Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
  13. 13Science Unit, International Vaccine Institute, Seoul, Republic of Korea
  14. 14Department of Microbiology, Institute for Viral Diseases, Biosafety Center, Korea University College of Medicine, Seoul, Republic of Korea
  15. 15Laboratory of Avian Diseases, Research Institute for Veterinary Science, and BK 21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
  16. 16Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, ChunCheon, Republic of Korea
  17. 17Laboratory of Veterinary Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
  18. 18Institute of Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
  19. 19Department of Microbiology, Yonsei University College of Medicine, Seoul, Republic of Korea
  20. 20Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
  21. 21Department of Nuclear Medicine, Seoul National University, College of Medicine, Seoul, Republic of Korea
  22. 22Department of Biochemistry, College of Life Science & Biotechnology, Brain Korea 21 PLUS Program, Initiative for Biological Functions & Systems, Yonsei University, Seoul, Republic of Korea
  23. 23BIO MAX Institute, Seoul National University, Seoul, Republic of Korea

Abstract

Understanding dynamic activations of pathophysiological processes in the infected lungs is important for effective treatment of SARS-CoV-2 infection. Time-course transcriptome analyses of infected lungs have been performed to address this issue. Since proteins actually execute the pathophysiological processes, however, the time-course transcriptome data provide limited information regarding their temporal transitions. Here, we present time-course proteomic profiling of lung tissues from K18-hACE2 transgenic mice using liquid chromatography-tandem mass spectrometry analysis at day 0, 1, 2, 5, and 7 after SARS-CoV-2 infection. Clustering analysis to identify early, intermediate, and late up-regulated proteins, analysis of pathways enriched by these proteins, and network analysis of early, intermediate, and late upregulated pathways revealed detailed dynamic activations of molecular networks perturbed upon infection, and further proposed five markers that represented early-to-intermediate activation of nonsense-mediated decay (Smg6 and Upf1), intermediate-to-late activation of phagocytosis (Fcgr4 and Lamp2), and late activation of neutrophil extracellular trap formation (Padi4) that could be associated with severe pathological transitions. Immunohistochemistry analysis confirmed these temporal upregulation patterns of the five markers identified from the time-course proteome data, and immunofluorescence analysis further confirmed that Padi4 was up-regulated predominantly in neutrophils at the late stage. Our temporal proteomic analysis suggests potential pathways and molecule markers that can be used to predict severe pathological transitions during the course of SARS-CoV-2 infection.

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BibTeX
@article{han2026temporal,
  title = {{Temporal Proteomic Characterization of SARS-CoV-2-Infected Mouse Lungs}},
  author = {Geun Hee Han and Misol Do and Dain On and Haengdueng Jeong and Jeong Jin Kim and Dohyun Han and Dongyoon Shin and Kyunggon Kim and Jung Seon Seo and Sung-Hee Kim and Jiseon Kim and Donghun Jeon and Hyuna Noh and Suhyeon Yoon and Sang Gyu Lee and Hyo-Jung Lee and Hong Bin Kim and Manki Song and Man-Seong Park and Kang-Seuk Choi and Jun Won Park and Jun-Won Yun and Jeon-Soo Shin and Ho-Young Lee and Hyuk Wan Ko and Jun-Young Seo and Ki Taek Nam and Daehee Hwang and Youngsoo Kim and Je Kyung Seong},
  journal = {Molecular \& Cellular Proteomics : MCP},
  year = {2026},
  month = jul,
  doi = {10.1016/j.mcpro.2026.101618},
  url = {https://doi.org/10.1016/j.mcpro.2026.101618},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Temporal Proteomic Characterization of SARS-CoV-2-Infected Mouse Lungs
AU  - Geun Hee Han
AU  - Misol Do
AU  - Dain On
AU  - Haengdueng Jeong
AU  - Jeong Jin Kim
AU  - Dohyun Han
AU  - Dongyoon Shin
AU  - Kyunggon Kim
AU  - Jung Seon Seo
AU  - Sung-Hee Kim
AU  - Jiseon Kim
AU  - Donghun Jeon
AU  - Hyuna Noh
AU  - Suhyeon Yoon
AU  - Sang Gyu Lee
AU  - Hyo-Jung Lee
AU  - Hong Bin Kim
AU  - Manki Song
AU  - Man-Seong Park
AU  - Kang-Seuk Choi
AU  - Jun Won Park
AU  - Jun-Won Yun
AU  - Jeon-Soo Shin
AU  - Ho-Young Lee
AU  - Hyuk Wan Ko
AU  - Jun-Young Seo
AU  - Ki Taek Nam
AU  - Daehee Hwang
AU  - Youngsoo Kim
AU  - Je Kyung Seong
PY  - 2026
DA  - 2026/07/02
JO  - Molecular & Cellular Proteomics : MCP
DO  - 10.1016/j.mcpro.2026.101618
UR  - https://doi.org/10.1016/j.mcpro.2026.101618
AB  - Understanding dynamic activations of pathophysiological processes in the infected lungs is important for effective treatment of SARS-CoV-2 infection. Time-course transcriptome analyses of infected lungs have been performed to address this issue. Since proteins actually execute the pathophysiological processes, however, the time-course transcriptome data provide limited information regarding their temporal transitions. Here, we present time-course proteomic profiling of lung tissues from K18-hACE2 transgenic mice using liquid chromatography-tandem mass spectrometry analysis at day 0, 1, 2, 5, and 7 after SARS-CoV-2 infection. Clustering analysis to identify early, intermediate, and late up-regulated proteins, analysis of pathways enriched by these proteins, and network analysis of early, intermediate, and late upregulated pathways revealed detailed dynamic activations of molecular networks perturbed upon infection, and further proposed five markers that represented early-to-intermediate activation of nonsense-mediated decay (Smg6 and Upf1), intermediate-to-late activation of phagocytosis (Fcgr4 and Lamp2), and late activation of neutrophil extracellular trap formation (Padi4) that could be associated with severe pathological transitions. Immunohistochemistry analysis confirmed these temporal upregulation patterns of the five markers identified from the time-course proteome data, and immunofluorescence analysis further confirmed that Padi4 was up-regulated predominantly in neutrophils at the late stage. Our temporal proteomic analysis suggests potential pathways and molecule markers that can be used to predict severe pathological transitions during the course of SARS-CoV-2 infection.
SN  - 1535-9476
SN  - 1535-9484
ER  -