PXD035254-1

PXD035254 is an original dataset announced via ProteomeXchange.

Title	IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses
Description	Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that limits viral pathogenesis and exerts poorly understood immunoregulatory functions. Here, using human and mouse models, we demonstrate that IFITM3 promotes MyD88-dependent, TLR-mediated IL-6 production following exposure to cytomegalovirus (CMV). IFITM3 also restricts IL-6 production in response to influenza and SARS-CoV-2. In dendritic cells, IFITM3 binds to the reticulon 4 isoform Nogo-B and promotes its proteasomal degradation. We reveal that Nogo-B mediates TLR-dependent pro-inflammatory cytokine production and promotes viral pathogenesis in vivo, and in the case of TLR2 responses, this process involves alteration of TLR2 cellular localization. Nogo-B deletion abrogates inflammatory cytokine responses and associated disease in virus-infected IFITM3-deficient mice. Thus, we uncover Nogo-B as a driver of viral pathogenesis and highlight an immunoregulatory pathway in which IFITM3 fine-tunes the responsiveness of myeloid cells to viral stimulation.
HostingRepository	PRIDE
AnnounceDate	2022-07-28
AnnouncementXML	Submission_2022-07-28_08:36:35.512.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robin Antrobus
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-11 13:50:13	ID requested
⏵ 1	2022-07-28 08:36:35	announced

Dataset with its publication pending

submitter keyword: viral pathogenesis, SILAC, IP-mass spec

Professor Ian Humphreys
contact affiliation	Division of Infection and Immunity/Systems Immunity University Research Institute, Cardiff University
contact email	Humpreysir@cardiff.ac.uk
lab head
Robin Antrobus
contact affiliation	CIMR medicine
contact email	pra29@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035254
     1. Label: PRIDE project
     2. Name: IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses