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| Status |
Public on Dec 02, 2023 |
| Title |
COVID-19 and influenza infections mediate distinct pulmonary cellular and transcriptomic changes [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
SARS-CoV-2 infection can cause persistent respiratory sequelae, as seen in long COVID. However, the underlying mechanisms remain unclear. To investigate pulmonary cellular and transcriptomic changes mediated by SARS-CoV-2 and influenza infection, we characterized the SARS-CoV-2-infected K18-hACE2 (K18) mice and compared their lung recovery with a mouse-adapted influenza model and verified the finding in SARS-CoV-2-infected nonhuman primates and in fatal human COVID-19 cases. K18-hACE2 mice infected with a sub-lethal dose of SARS-CoV-2 lost body weight from 1 - 8 days post-infection (DPI), and then gradually returned to baseline weight between 8 -13 DPI. Infected mice showed patchy pneumonia associated with histiocytic inflammation, collagen deposition, and increased pulmonary interferon and inflammatory response signature gene changes at 21 and 45 DPI. Transcriptomic analyses revealed that compared to influenza-infected mice, SARS-CoV-2-infected mice had reduced interferon-gamma/alpha responses at 4 DPI and failed to induce keratin 5 (Krt5) at 6 DPI in lung, a marker of nascent pulmonary progenitor cells. They also showed reduced activation of epithelial-to-mesenchymal transition and apical junction pathways compared to influenza (Flu)-infected mice. Histologically, influenza- but not SARS-CoV-2- infected mice showed extensive Krt5+ “pods” structure co-stained with stem cell markers Trp63/ NGFR proliferated in the pulmonary consolidation area at both 7 and 14 DPI, with regression at 21 DPI. These Krt5+ “pods” and proliferative stem cells were not observed in SARS-CoV-2 infection in the lungs of humans or nonhuman primates. These results suggest that SARS-CoV-2 infection fails to induce nascent Krt5+ cell proliferation in consolidated regions, leading to incomplete repair of the injured lung which may underlie the persistent clinical symptoms of long COVID.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for COVID mice at 4DPI, 6DPI and 21DPI and Influenza infected mice.
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| Contributor(s) |
Wang C, Shamima Khatun M, Zhang Z, Allen MJ, Chen Z, Ellsworth CR, Currey JM, Dai G, Tian D, Bach K, Yin X, Traina-Dorge V, Rappaport J, Maness NJ, Blair RV, Kolls JK, Pociask DA, Qin X |
| Citation(s) |
38092883 |
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| Submission date |
Nov 28, 2023 |
| Last update date |
Jan 02, 2024 |
| Contact name |
Jay Kolls |
| Organization name |
Tulane University
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| Department |
Medicine
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| Lab |
Center for Translational Research in Infection and Inflammation
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| Street address |
1430 Tulane Ave
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| City |
New Orleans |
| State/province |
LA |
| ZIP/Postal code |
70112 |
| Country |
USA |
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| Platforms (1) |
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| Samples (21)
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| GSM7919722 |
K18-hACE2, SARS-CoV-2, Day21_1_bulk RNA |
| GSM7919723 |
K18-hACE2, SARS-CoV-2, Day21_2_bulk RNA |
| GSM7919724 |
K18-hACE2, SARS-CoV-2, Day21_3_bulk RNA |
| GSM7919725 |
K18-hACE2, naïve_1_bulk RNA |
| GSM7919726 |
K18-hACE2, naïve_2_bulk RNA |
| GSM7919727 |
K18-hACE2, naïve_3_bulk RNA |
| GSM7919728 |
K18-hACE2, naïve_4_bulk RNA |
| GSM7919729 |
K18-hACE2, SARS-CoV-2, Day4_1_bulk RNA |
| GSM7919730 |
K18-hACE2, SARS-CoV-2, Day4_2_bulk RNA |
| GSM7919731 |
K18-hACE2, SARS-CoV-2, Day4_3_bulk RNA |
| GSM7919732 |
K18-hACE2, SARS-CoV-2, Day6_1_bulk RNA |
| GSM7919733 |
K18-hACE2, SARS-CoV-2, Day6_2_bulk RNA |
| GSM7919734 |
K18-hACE2, SARS-CoV-2, Day6_3_bulk RNA |
| GSM7919735 |
K18-hACE2, PR8, Day4_1_bulk RNA |
| GSM7919736 |
K18-hACE2, PR8, Day4_2_bulk RNA |
| GSM7919737 |
K18-hACE2, PR8, Day4_3_bulk RNA |
| GSM7919738 |
K18-hACE2, PR8, Day4_4_bulk RNA |
| GSM7919739 |
K18-hACE2, PR8, Day6_1_bulk RNA |
| GSM7919740 |
K18-hACE2, PR8, Day6_2_bulk RNA |
| GSM7919741 |
K18-hACE2, PR8, Day6_3_bulk RNA |
| GSM7919742 |
K18-hACE2, PR8, Day6_4_bulk RNA |
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| This SubSeries is part of SuperSeries: |
| GSE248778 |
COVID-19 and influenza infections mediate distinct pulmonary cellular and transcriptomic changes |
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| Relations |
| BioProject |
PRJNA1045984 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248773_CoV_K18_21dpi_Vs.CoV_K18_4dpi.csv.gz |
54.6 Kb |
(ftp)(http) |
CSV |
| GSE248773_Flu_K18_4dpi_Vs.CoV_K18_4dpi.csv.gz |
234.9 Kb |
(ftp)(http) |
CSV |
| GSE248773_Flu_K18_4dpi_vs_CoV_K18_4dpi_Naive.csv.gz |
553.3 Kb |
(ftp)(http) |
CSV |
| GSE248773_Flu_K18_6dpi_Vs.CoV_K18_6dpi.csv.gz |
205.4 Kb |
(ftp)(http) |
CSV |
| GSE248773_Flu_K18_6dpi_vs_CoV_K18_6dpi_Naive.csv.gz |
719.3 Kb |
(ftp)(http) |
CSV |
| GSE248773_K18_CoV_21dpi_vs_K18_Naive.csv.gz |
51.8 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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