PXD080823-1

PXD080823 is an original dataset announced via ProteomeXchange.

Title	Nuclear activities and interactome of the NS5 protein of Tick-Borne Encephalitis Virus
Description	Orthoflaviviruses are RNA viruses responsible for significant diseases in humans, domesticated animals and wildlife. Their NS5 protein is central in viral replication, functioning both as an RNA-dependent RNA polymerase and a methyltransferase, while also modulating cellular processes, including the interferon response. Although viral replication is cytoplasmic, the NS5 protein of several mosquito-borne orthoflaviviruses cycles between the cytoplasm and the nucleus of infected human cells. However, the nuclear localization and function of NS5 of tick-borne orthoflaviviruses, such as tick-borne encephalitis virus (TBEV), remained poorly understood. Microscopy analysis and cell fractionation revealed that the NS5 protein of TBEV localized to both the cytoplasm and nucleoplasm of infected cells. Mutagenesis studies identified critical residues required for its nuclear targeting. Mutating these residues in a TBEV replicon abolished viral replication. Immunoprecipitation-mass spectrometry analyses performed in two human cell lines infected with TBEV recovered 352 NS5 partners. Among them, 187 were nuclear or partially nuclear. By integrating our interactome data with that of Powassan virus (POWV), another tick-borne orthoflavivirus, we refined a list of 20 high-confidence NS5 partners, including splicing factors and chromatin modulators. Functional analysis revealed that seven of these nuclear partners significantly modulated viral replication, further underscoring the importance of nuclear NS5 in the viral life cycle. Our work advances our understanding of the nuclear function of the NS5 proteins of tick-borne orthoflaviviruses.
HostingRepository	PRIDE
AnnounceDate	2026-07-28
AnnouncementXML	Submission_2026-07-27_22:26:24.369.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeffrey Johnson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-09 13:17:11	ID requested
⏵ 1	2026-07-27 22:26:24	announced

Dataset with its publication pending

submitter keyword: TBEV, IP-MS, NS5

Jeffrey Johnson
contact affiliation	Icahn School of Medicine at Mount Sinai
contact email	jeffrey.johnson@mssm.edu
lab head
Jeffrey Johnson
contact affiliation	Icahn School of Medicine at Mount Sinai
contact email	jeffrey.johnson@mssm.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD080823
     1. Label: PRIDE project
     2. Name: Nuclear activities and interactome of the NS5 protein of Tick-Borne Encephalitis Virus