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GEO help: Mouse over screen elements for information. |
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Status |
Public on Apr 15, 2024 |
Title |
Murine Model of Long- COVID19 following SARS-CoV-2 Variant Infection |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. We studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies, in surviving mice up to 4 months post-acute infection, revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. Surviving mice showed no detectable viral RNA in the brain and minimal neuroinflammation post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and reduced levels of genes associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent T helper 1 prone cellular immune responses and high neutralizing antibodies in the periphery for months post-acute infection. Overall, infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long COVID patients.
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Overall design |
6- to 8-week-old K18-hACE2 mice were infected intranasally with 600PFU of SARS-CoV-2 Delta strain. At 1-month (n =4), and 4-months (n=3) post infection, brain samples were collected for RNA extraction. PBS-infected mice (n=4) were collected at 4-month as mock-samples for comparison.
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Contributor(s) |
Singh A, Wang T, Adam A |
Citation(s) |
38765009 |
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Submission date |
Feb 29, 2024 |
Last update date |
May 30, 2024 |
Contact name |
Haiping Hao |
E-mail(s) |
hahao@UTMB.EDU
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Phone |
4097726349
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Organization name |
University of Texas Medical Branch
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Department |
Biochemistry and Molecular Biology
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Street address |
1005 strand st
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City |
Galveston |
State/province |
Texas |
ZIP/Postal code |
77555 |
Country |
USA |
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Platforms (1) |
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Samples (11)
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GSM8121257 |
AS4, brain, Mock-infected |
GSM8121259 |
AS5, brain, Delta-variant infected 4 month |
GSM8121261 |
AS6, brain, Delta-variant infected 4 month |
GSM8121264 |
AS7, brain, Delta-variant infected 4 month |
GSM8121268 |
AS13, brain, Delta-variant infected 1 month |
GSM8121270 |
AS14, brain, Delta-variant infected 1 month |
GSM8121272 |
AS15, brain, Delta-variant infected 1 month |
GSM8121273 |
AS16, brain, Delta-variant infected 1 month |
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Relations |
BioProject |
PRJNA1082367 |
Supplementary file |
Size |
Download |
File type/resource |
GSE260625_all.counts.tsv.gz |
717.8 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
Raw data are available in SRA |
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