<<< Full experiment listing

PXD028123

PXD028123 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePhosphoproteome of SARS-CoV-2 infected Human Nasal Epithelium
DescriptionThe nasal epithelium is the primary initial site of SARS-CoV-2 entry in the human body. Since much of the molecular detail defining coronavirus entry and replication was derived from non-nasal cell lines, it remains unclear how SARS-CoV-2 overcomes the physical nasal mucus and periciliary mucin layers to infect and spread through the nasal epithelium. Using air-liquid interface cultured primary nasal epithelial cells, we observed that SARS-CoV-2 attaches to motile cilia during the initial stage of infection. Depletion of cilia inhibited SARS-CoV-2, as well as respiratory syncytial virus and parainfluenza virus infection, suggesting a widely-used ciliary mechanism for respiratory viral entry. Using electron and immunofluorescence microscopy, we further observed that SARS-CoV-2 progeny virions attached to airway microvilli 24 hours post infection and triggered the formation of apically extended and highly branched microvilli that organize viral egress from the microvillar base back into the mucus layer, supporting a model of virus dispersion throughout airway tissue via mucociliary transport. Chemical perturbation of microvillus formation severely impaired viral egress and subsequent spread. Phosphoproteomic analyses indicate that virally-triggered microvillar branching is linked to the p21-activated kinase 1 and 4 (PAK1/4) signaling pathway and viral infection is impaired by PAK1/4 kinase inhibitors. Our work provides insight into the mechanisms by which SARS-CoV-2 and potentially many respiratory viruses penetrate the physical nasal epithelium barrier, a first line of defense against pathogens, thus revealing a new view of the motile cilia and microvilli as critical host factors required for viral entry and egress.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:33:41.731.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD028123
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJanos Demeter
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; acetylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-08-25 04:04:35ID requested
12023-03-10 16:18:39announced
22023-11-14 08:33:42announced2023-11-14: Updated project metadata.
Publication List
10.6019/PXD028123;
Wu CT, Lidsky PV, Xiao Y, Cheng R, Lee IT, Nakayama T, Jiang S, He W, Demeter J, Knight MG, Turn RE, Rojas-Hernandez LS, Ye C, Chiem K, Shon J, Martinez-Sobrido L, Bertozzi CR, Nolan GP, Nayak JV, Milla C, Andino R, Jackson PK, SARS-CoV-2 replication in airway epithelia requires motile cilia and microvillar reprogramming. Cell, 186(1):112-130.e20(2023) [pubmed]
Keyword List
ProteomeXchange project tag: Covid-19
submitter keyword: SARS-CoV-2, human nasal epithelium, phosphoproteome
Contact List
Peter K. Jackson
contact affiliationBaxter Laboratory for Stem Cell Biology Department of Microbiology & Immunology Stanford University School of Medicine 269 Campus Drive Stanford, CA 94305-5175, USA
contact emailpjackson@stanford.edu
lab head
Janos Demeter
contact affiliationStanford University
contact emailjdemeter@stanford.edu
dataset submitter
Full Dataset Link List
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/2023/03/PXD028123
PRIDE project URI
Repository Record List
[ + ]