PXD025851

PXD025851 is an original dataset announced via ProteomeXchange.

Title	Upregulation of USP18-ISG15 axis associates with protective immune responses and limited histopathology during SARS-CoV2 infection of the human lung
Description	Investigating the intra-lung human immune responses to SARS-CoV-2, and how immune signatures temporally correlate to distinct histopathological manifestations of disease in the human lung, is not possible in human patients. While current non-human primate and rodent models have proven instrumental for evaluating COVID-19 treatments and vaccines, their non-human nature precludes faithful recapitulation of fundamental host-pathogen interactions and immunopathogenesis, particularly those governing severe COVID-19 disease. Here, using different mouse models engrafted with human lung tissues and human immune hematopoietic cells, we provide a unique picture of how differential human hematopoietic reconstitution, and immune signatures upon infection, correlate with distinct histopathology during SARS-CoV-2 infection. To do so, we engrafted pairs of human fetal lung xenografts (fLX) harboring lung-resident hematopoietic lineages into immunodeficient NRG mice (NRG-L), or into NRG-Flk2-/-Flt3LG mice co-engrafted with components of a human immune system (HIS-NRGF-L). Strikingly, while SARS-CoV-2 inoculation of NRG-L mice resulted in productive infection and extensive histopathological features typically observed in the lungs of severe COVID-19 patients, HIS-NRGF-L were able to rapidly control infection while preserving tissue integrity. Distinct histopathological outcomes were governed by differential proteomics and phospho-proteomics signatures and underscored the USP18-ISG15 pathway as a top immunomodulatory pathway defining effective control of viral replication and maintenance of tissue integrity in human lung tissue during SARS-CoV-2 infection. Our work highlights fLX-engrafted mice as a powerful platform to investigate the molecular basis that drives effective immune control of SARS-CoV-2, and open avenues for the development of innovative immunotherapies targeting the USP18-ISG15 pathway to alleviate severe COVID-19.
HostingRepository	PRIDE
AnnounceDate	2024-10-08
AnnouncementXML	Submission_2024-10-08_11:36:34.398.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ryan Hekman
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-06 23:39:59	ID requested
⏵ 1	2024-10-08 11:36:34	announced

10.1016/J.CELREP.2022.110714;

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: lung fetal xenograft,humanized mice, SARS-CoV-2, COVID19

Florian Douam
contact affiliation	Boston University
contact email	fdouam@bu.edu
lab head
Ryan Hekman
contact affiliation	Boston University
contact email	rhekman@bu.edu
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2022/04/PXD025851

PRIDE project URI

• PRIDE
  1. PXD025851
     1. Label: PRIDE project
     2. Name: Upregulation of USP18-ISG15 axis associates with protective immune responses and limited histopathology during SARS-CoV2 infection of the human lung