PXD040525-1
PXD040525 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | An ex vivo human precision-cut lung slice platform provides insight into SARS-CoV-2 pathogenesis and for evaluating antiviral drugs |
| Description | COVID-19 has claimed millions of lives since the emergence of SARS-CoV-2, and lung disease appears the primary cause of the deaths in COVID-19 patients. However, the underlying mechanisms of COVID-19 pathogenesis remain elusive and there is no existing model where the disease can be faithfully recapitulated and conditions for the infection process can be experimentally controlled. Herein we report the establishment of an ex vivo human precision-cut lung slice (hPCLS) platform for studying SARS-CoV-2 pathogenicity and innate immune response, and for evaluating the efficacy of antiviral drugs against SARS-CoV-2. We show that while SARS-CoV-2 continued to replicate during the course of infection, infectious virus production peaked within 2 days, and rapidly declined thereafter. Although most proinflammatory cytokines examined were induced by SARS-CoV-2 infection, the degree of induction and types of cytokines varied significantly among hPCLS from individual donors, which might reflect the heterogeneity of human populations. In particular, two cytokines (IL-8 and IP-10) are highly and consistently induced, suggesting a role in the pathogenesis of COVID-19. Histopathological examination reveals focal cytopathic effects late in the infection, which are largely limited to type II alveolar cells. Transcriptomic and proteomic analyses identified molecular signatures and cellular pathways that are largely consistent with the progression of COVID-19 in patients. Furthermore, we show that homoherringtonine, a natural plant alkaloid derived from Cephalotoxus fortunei, not only inhibited virus replication but also inflammatory cytokines, and ameliorated the histopathological changes of the lungs caused by SARS-CoV-2, demonstrating the usefulness of the hPCLS platform for evaluating antiviral drugs. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-06-21 |
| AnnouncementXML | Submission_2024-06-21_06:49:03.502.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Stephanie Byrum |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Oxidation; Carbamidomethyl |
| Instrument | Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-03-01 05:53:17 | ID requested | |
| ⏵ 1 | 2024-06-21 06:49:03 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: SARS-CoV-2, hPCLS |
Contact List
| Xuming Zhang | |
|---|---|
| contact affiliation | University of Arkansas for Medical Sciences |
| contact email | zhangxuming@uams.edu |
| lab head | |
| Stephanie Byrum | |
| contact affiliation | University of Arkansas for Medical Sciences |
| contact email | sbyrum@uams.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/v05/MSV000091383/ |
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