PXD041488

PXD041488 is an original dataset announced via ProteomeXchange.

Title	Prolyl hydroxylation is required for maturation and secretion of Zika virus non-structural protein 1
Description	Mosquito-borne flaviviruses such as Zika virus (ZIKV) and dengue virus (DENV) have a high epidemic potential and are associated with a wide range of possible outcomes, from asymptomatic infections to severe complications. The flavivirus non-structural protein 1 (NS1), which can be membrane-bound as well as secreted from the cell, plays important roles in viral replication, immune evasion and pathogenesis. To identify the interactome of ZIKV NS1, we infected Huh7 and neural progenitor cells with recombinant ZIKV encoding a FLAG-tagged NS1 and analysed the binding partners with quantitative mass spectrometry. In both cell types, multiple prolyl hydroxylase enzymes were identified as NS1 interactors and mass spectrometry data showed that NS1 contains potential hydroxyproline residues at positions 181, 267 and 281, indicating that these enzymes are involved in post-translational modification of NS1. Chemical inhibition of prolyl hydroxylase enzymes reduced ZIKV RNA levels and titers, as well as NS1 glycosylation, plasma membrane localization and secretion. Mutagenesis of the proline residue at position 281 moderately impaired proper expression of NS1, although viral replication was unaffected. In contrast, substituting proline at position 267 strongly dysregulated NS1 expression and reversions to the wild-type sequence were observed already after passage 1, suggesting that this mutation leads to severe replication defects. Our results identify prolyl hydroxylation as an essential post-translational modification of ZIKV NS1.
HostingRepository	PRIDE
AnnounceDate	2025-01-28
AnnouncementXML	Submission_2025-01-28_00:34:27.471.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pascal Jansen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	hydroxylated proline; amidated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-12 05:03:52	ID requested
⏵ 1	2025-01-28 00:34:27	announced

Dataset with its publication pending

submitter keyword: host-pathogen interactions, NS1, prolyl hydroxylase,Zika virus, hydroxyproline

Ronald Pieter van Rij
contact affiliation	Dept. Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
contact email	ronald.vanrij@radboudumc.nl
lab head
Pascal Jansen
contact affiliation	Radboud University
contact email	p.jansen@science.ru.nl
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/2025/01/PXD041488

PRIDE project URI

• PRIDE
  1. PXD041488
     1. Label: PRIDE project
     2. Name: Prolyl hydroxylation is required for maturation and secretion of Zika virus non-structural protein 1