PXD041663

PXD041663 is an original dataset announced via ProteomeXchange.

Title	Endogenous pull-downs of human proteins ATP6V1A and AHNAK to validate interactions with influenza A virus proteins M2 and NEP by targeted mass spectrometry in virus-infected cells
Description	Influenza A Virus (IAV) is a recurring respiratory virus with antiviral therapies of limited use. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry (AP-MS) and global phosphoproteomic and protein abundance analyses with three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we mapped 332 IAV-human protein-protein interactions (PPIs) and identified 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza revealed several genes, including the structural scaffold protein AHNAK, with predicted loss-of-function variants that were also identified in our proteomic analyses. Of our identified host factors, 54 significantly altered IAV infection upon siRNA knockdown, and two factors, COPB1 and AHNAK, were also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppressed IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. This project includes endogenous IP data from A549 cells and NHBE cells infected with H5N1 IAV validating IAV-host PPIs M2-ATP6V1A and NEP-AHNAK, respectively. M2-ATP6V1A and NEP-AHNAK PPIs were first identified in AP-MS data that is submitted under its own dataset identifier (PXD036077).
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:57:44.144.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kelsey Haas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-19 17:39:11	ID requested
1	2023-07-25 15:47:12	announced
⏵ 2	2024-10-22 05:57:44	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: virus-host,Protein-protein interaction, H5N1, PRM, Human, A549, NHBE, Influenza A Virus

Robyn Kaake
contact affiliation	Dept. Cellular and Molecular Pharmacology, University of California - San Francisco (UCSF), USA
contact email	robyn.kaake@gladstone.ucsf.edu
lab head
Kelsey Haas
contact affiliation	Department of Cellular & Molecular Pharmacology, University of California San Francisco
contact email	kelsey.haas@gladstone.ucsf.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/2023/07/PXD041663

PRIDE project URI

• PRIDE
  1. PXD041663
     1. Label: PRIDE project
     2. Name: Endogenous pull-downs of human proteins ATP6V1A and AHNAK to validate interactions with influenza A virus proteins M2 and NEP by targeted mass spectrometry in virus-infected cells