PXD018419-1

PXD018419 is an original dataset announced via ProteomeXchange.

Title	Influenza A virus-triggered succinylation in lung epithelial cells
Description	Influenza A virus (IAV) is the etiological agent of a highly contagious acute respiratory disease, which causes a considerable socioeconomic burden despite annual vaccination campaigns. Therefore, it is essential to better understand IAV-host cells interaction to help design innovative antiviral therapies. In that regard, recent studies revealed the interplay between metabolic and immune signaling pathways. However, it remains unknown whether IAV alters lung tissues metabolism and what is its potential functional consequence. Using in vitro and in vivo models as well as human respiratory fluids and in-depth metabolomics analysis, we first found that IAV infection alters the glycolysis and mitochondrial oxidative respiration in lung tissues, leading to the accumulation of several immunometabolites in the bronchoalveolar airspaces. We next focused on one mitochondria-derived metabolite, i.e. succinate as its accumulation was found not only in the lungs of IAV-challenged mice but also in the tracheal fluids of IAV-infected patients. Remarkably, we found that succinate exhibits a potent antiviral activity both in vitro and in vivo as it inhibits H1N1 and H3N2 IAV strains and it strongly decreases IAV-triggered inflammatory response. The underlying inhibiting mechanism involves a disruption of IAV replication cycle. Indeed, succinate prevents specifically the nuclear export of the viral nucleoprotein NP, likely due to a specific succinylation at K87 site. Finally, we showed that mice receiving succinate through the intranasal route are more resistant to IAV pneumonia than mock-treated animals. Hence, our study identifies the metabolite succinate as a novel component of the host antiviral arsenal.
HostingRepository	PRIDE
AnnounceDate	2022-03-24
AnnouncementXML	Submission_2022-03-24_00:37:37.387.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Valentin SABATET
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	succinylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-07 07:52:48	ID requested
⏵ 1	2022-03-24 00:37:37	announced
2	2024-10-22 05:35:33	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: influenza virus, succinylation

Damarys Loew
contact affiliation	Head of the Curie Institute Mass Spectrometry Platform
contact email	damarys.loew@curie.fr
lab head
Valentin SABATET
contact affiliation	Curie Institute
contact email	valentin.sabatet@curie.fr
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/2022/03/PXD018419

PRIDE project URI

• PRIDE
  1. PXD018419
     1. Label: PRIDE project
     2. Name: Influenza A virus-triggered succinylation in lung epithelial cells