PXD054178

PXD054178 is an original dataset announced via ProteomeXchange.

Title	Molluscum Contagiosum Virus Protein MC089 Inhibits Interferon Regulatory Factor 3 Activation
Description	Molluscum contagiosum virus (MCV) is a human-specific poxvirus that causes a highly common but mild infection characterised by distinctive and persistent papular skin lesions. These lesions can persist for long periods without an effective clearance response from the host. MCV, like all poxviruses, encodes multiple known immunosuppressive proteins which target innate immune signalling pathways involved in viral nucleic acid sensing, interferon production and inflammation which should trigger antiviral immunity leading to clearance. Two major families of transcription factors responsible for driving the immune response to viruses are the nuclear factor kappa B (NF-κB) and the Interferon Regulatory Factor (IRF) families. Whilst NF-κB broadly drives pro-inflammatory gene expression and IRFs chiefly drive interferon induction, both collaborate in transactivating many of the same genes in a concerted immune response to viral infection. Here we report that the MCV protein MC089 specifically inhibits IRF activation from both DNA and RNA sensing pathways making it the first characterized MCV inhibitor to selectively target IRF activation to date. MC089 interacts with proteins required for IRF activation, namely IKKε, TBKBP1 and NAP1. Additionally, MC089 targets RNA sensing by associating with the RNA sensing adaptor protein MAVS on mitochondria. MC089 displays specificity in its inhibition of IRF3 activation by suppressing immunostimulatory nucleic acid-induced serine 396 phosphorylation without affecting the phosphorylation of serine 386. The selective interaction of MC089 with IRF-regulatory proteins and site-specific inhibition of IRF3 phosphorylation may offer a tool to provide novel insights into the biology of IRF3 regulation.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-24_16:11:29.569.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jyoti Vishwakarma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-24 06:06:45	ID requested
⏵ 1	2025-08-24 16:11:30	announced

10.1099/jgv.0.002015;

Al Hamrashdi M, Sanchez Perez C, Haas DA, Vishwakarma J, Pichlmair A, Bowie AG, Brady G, Molluscum contagiosum virus protein MC089 inhibits interferon regulatory factor 3 activation. J Gen Virol, 105(8):(2024) [pubmed]

submitter keyword: Molluscum Contagiosum Virus

MC089

Innate Immunity

IKKε

TBKBP1

NAP1

MAVS.

Andreas Pichlmair
contact affiliation	Immunopathology of Virus Infections Laboratory, Institute of Virology, Technical University of Munich, Schneckenburgerstr. 8, D-81675 Munich, Germany (Lab head)
contact email	andreas.pichlmair@tum.de
lab head
Jyoti Vishwakarma
contact affiliation	Masters in Biotechnology
contact email	jyoti.vishwakarma@tum.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/2025/08/PXD054178

PRIDE project URI

• PRIDE
  1. PXD054178
     1. Label: PRIDE project
     2. Name: Molluscum Contagiosum Virus Protein MC089 Inhibits Interferon Regulatory Factor 3 Activation