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Status |
Public on Jun 28, 2024 |
Title |
Respiratory SARS-CoV-2 Infection Induces Skeletal Muscle Atrophy and Long-Lasting Energy Metabolism Suppression |
Organism |
Mesocricetus auratus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts human health beyond acute infection. Myalgia and fatigue represent two of the most prevalent symptoms in post-COVID-19 syndrome. To determine the mechanisms underlying prolonged muscle symptoms, we characterized longitudinal histopathological and transcriptional changes of skeletal muscle after acute respiratory SARS-CoV-2 infection in a COVID-19 hamster model and compared them with respiratory influenza A virus (IAV) infection. Histopathological and bulk RNA sequencing analyses at 3, 30, and 60 days post infection (dpi) showed no evidence of direct viral invasion, inflammatory cell infiltration, or microthrombi in skeletal muscle, but myofiber atrophy was observed in the SARS-CoV-2 group at 60 dpi, accompanied by downregulation of myofiber genes, atrogenes, and cytoplasmic ribosomal protein genes, and upregulation of autophagy genes. There was persistent downregulation of genes involved in mitochondrial oxidative phosphorylation, fatty acid beta-oxidation, and tricarboxylic acid cycle in the SARS-CoV-2 but not the IAV group. Moreover, TNF-alpha/NF-kB and TGF-beta signaling pathways were differentially regulated in the SARS-CoV-2 group. Our findings suggest that persistent muscle symptoms after COVID-19 may be caused by muscle atrophy and energy metabolism suppression, and that the systemic inflammatory cytokine response may contribute, in part, to the skeletal muscle abnormalities.
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Overall design |
Golden hamsters were intranasally administered PBS (mock-infected) or intranasally infected with 100,000 pfu of H1N1 influenza A virus (A/California/04/2009, IAV) or 1000 pfu SARS-CoV-2 (USA-WA1/2020), and RNA was extracted from the quadriceps muscle at 3 days (all infection groups) or at 30 or 60 days (IAV or SARS-CoV-2 infection groups only) and sequenced.
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Contributor(s) |
Homma ST, Zhou L |
Citation(s) |
39062017 |
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Submission date |
May 08, 2023 |
Last update date |
Aug 05, 2024 |
Contact name |
Boston University Microarray and Sequencing Resource |
E-mail(s) |
msrdata@bu.edu
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Organization name |
Boston University
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Department |
Microarray and Sequencing Resource
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Street address |
72 East Concord Street, E631
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02118 |
Country |
USA |
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Platforms (1) |
GPL33389 |
NextSeq 2000 (Mesocricetus auratus) |
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Samples (21)
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Relations |
BioProject |
PRJNA970225 |
Supplementary file |
Size |
Download |
File type/resource |
GSE231910_counts.txt.gz |
577.0 Kb |
(ftp)(http) |
TXT |
GSE231910_varianceStabilizingTransformation.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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