PXD039034

PXD039034 is an original dataset announced via ProteomeXchange.

Title	Quantitative temporal proteomic analysis of modified vaccinia Ankara, a mpox vaccine
Description	Modified vaccinia Ankara (MVA) immunisation is being deployed to curb the current outbreak of mpox in multiple countries1. Originally authorized for vaccination against smallpox, MVA is a vaccinia virus (VACV) strain that does not replicate in human cells or cause serious adverse events. Here, we conducted a highly multiplexed proteomic analysis2 to quantify >9,000 cellular proteins and ~80% of viral proteins at five time points throughout MVA infection of human cells3. 690 human proteins were down-regulated >2-fold by MVA, revealing a substantial remodelling of the host proteome. >25% of these MVA targets, including multiple components of the nuclear pore complex (NPC), were not shared with VACV-Western Reserve4, which is derived from a first generation smallpox vaccine associated with serious adverse events. Using pharmacological inhibition of viral DNA replication and heat-inactivated virions, we discovered that post-replicative gene expression is necessary for the downregulation of NPC proteins and for elements of MVA antagonism of innate immune sensing. Our approach thus provides the first global view of the impact of MVA infection on the host proteome, offers insights into how MVA interacts with the antiviral defences and identifies cellular mechanisms that may underpin the abortive infection of human cells. These discoveries will prove vital to the rational design of future generations of vaccines.
HostingRepository	PRIDE
AnnounceDate	2023-10-11
AnnouncementXML	Submission_2023-10-11_07:34:09.220.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MichaelWeekes
SpeciesList	scientific name: Modified Vaccinia Ankara virus; NCBI TaxID: 467144; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-21 06:08:07	ID requested
⏵ 1	2023-10-11 07:34:09	announced

Dataset with its publication pending

submitter keyword: modified vaccinia Ankara

vaccinia virus

mpox

monkeypox virus

innate immunity

immune evasion

host-pathogen interaction

proteomics

MichaelWeekes
contact affiliation	Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK
contact email	Mpw1001@cam.ac.uk
lab head
MichaelWeekes
contact affiliation	University of Cambridge
contact email	mpw1001@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039034
     1. Label: PRIDE project
     2. Name: Quantitative temporal proteomic analysis of modified vaccinia Ankara, a mpox vaccine