PXD081438-1

PXD081438 is an original dataset announced via ProteomeXchange.

Title	HSV-1 interferes with STAT3 expression in infected mature dendritic cells. Part 3
Description	Herpes simplex virus type 1 (HSV-1) is the prototype of the α-herpesvirus family. To propagate within the host organism, HSV-1 has evolved several strategies to subvert the host immune response. Due to the pivotal role of dendritic cells (DCs), bridging innate and adaptive immunity and activating naïve T cells, they represent an attractive target for HSV-1-triggered immune regulation. Here, we report a novel HSV-1-mediated mechanism of signal transducer and activator of transcription 3 (STAT3) dysregulation in human monocyte-derived mature DCs (mDCs). Due to STAT3’s antiviral activity, STAT3 was shown to be modulated by viruses to efficiently replicate in several different cell types, however, not in DCs. We show that HSV-1 infection of mDCs leads to diminished total STAT3 expression and STAT3 phosphorylation (pSTAT3), as well as downregulation of STAT3 mRNA very early upon infection. Protein downregulation of STAT3 could be verified by label-free mass spectrometric analysis of HSV-1- and HSV-2-infected mDCs. We found that two viral proteins, the tegument protein virion host shutoff (vhs) and the immediate early (IE) protein ICP27, contribute to STAT3 protein downregulation upon HSV-1 infection. However, HSV-1 Δvhs and ΔICP27 deletion strains still inhibited pSTAT3 in infected mDCs, suggesting that different viral proteins impair STAT3 phosphorylation and total STAT3. Moreover, STAT3 protein levels were degraded in a proteasome-dependent, but apoptosis-independent manner. Taken together, we demonstrate that HSV-1 downregulates STAT3 in HSV-1-infected human mDCs at the transcript, protein and phosphorylation levels. Downregulation of STAT3 protein depended on vhs and the proteasome, very likely to shape DC function for immune evasion and modulation.
HostingRepository	PRIDE
AnnounceDate	2026-07-22
AnnouncementXML	Submission_2026-07-21_22:35:22.036.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexandra Birzer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-21 19:49:56	ID requested
⏵ 1	2026-07-21 22:35:22	announced

10.1099/JGV.0.002280;

submitter keyword: immune modulation,STAT3, HSV-1, dendritic cell, IL-6 signaling pathway

Alexandra Birzer
contact affiliation	Harald zur Hausen Institute of Virology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
contact email	alexandra.birzer@uk-erlangen.de
lab head
Alexandra Birzer
contact affiliation	Harald-zur-Hausen-Institute für Virologie
contact email	alexandra.birzer@uk-erlangen.de
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/2026/07/PXD081438

PRIDE project URI

• PRIDE
  1. PXD081438
     1. Label: PRIDE project
     2. Name: HSV-1 interferes with STAT3 expression in infected mature dendritic cells. Part 3