PXD040525

PXD040525 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-01 05:53:17	ID requested
⏵ 1	2024-06-21 06:49:03	announced

no publication

submitter keyword: SARS-CoV-2, hPCLS

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

MassIVE dataset URI

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