PXD065223-1

PXD065223 is an original dataset announced via ProteomeXchange.

Title	Virion Proteomics of Genetically Intact HCMV Reveals a Novel Regulator of Envelope Glycoprotein Composition that Protects Against Humoral Immunity
Description	Human cytomegalovirus (HCMV) is a clinically important herpesvirus that has co-evolved for millions of years with its human host, and establishes lifelong persistent infection. A substantial proportion of its 235kb genome is dedicated to manipulating host immunity through targeting antiviral host proteins for degradation or relocalisation. Quantitative proteomics of the infected cell has extensively characterised these processes, but the cell-free virion has been less well studied. We therefore carried out proteomic analysis of a clinical HCMV strain (Merlin) virion. This revealed 18 novel components, including the viral protein gpUL141, which is recognised as an NK immune-evasin that targets several host proteins (CD155, CD112, and TRAILR) when expressed within the cell. Co-Immunoprecipitation of gpUL141 from virions identified interactions with viral entry glycoproteins from the trimer (gH/gL/gO), pentamer (gH/gL/UL128/UL130/UL131A), and gH/gpUL116 complexes, as well as gB. Only interactions with gH/gB occurred in the absence of other viral proteins. Analysis supported a model in which gpUL141 homodimers independently interacted with separate gB/gH-containing complexes. gpUL141 encodes an ER retention domain that restricts trafficking through the ER/golgi, and limited the transport of glycoprotein complexes bound by gpUL141. As a result, gpUL141 reduced levels of multiple glycoprotein complexes on the infected cell surface as well as in the virion. This reduced syncytium formation, inhibited antibody-dependent cellular cytotoxicity (ADCC), and reduced susceptibility to neutralising antibodies. Thus, gpUL141 represents an immune-evasin that not only targets host proteins to limit NK-cell attack, but also alters the trafficking of multiple viral glycoprotein complexes in order to evade humoral immunity.
HostingRepository	PRIDE
AnnounceDate	2026-02-06
AnnouncementXML	Submission_2026-02-06_09:12:25.891.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Weekes
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Human cytomegalovirus (HHV-5) (Human herpesvirus 5); NCBI TaxID: NEWT:10359;
ModificationList	6x(13)C labeled residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-19 08:44:12	ID requested
⏵ 1	2026-02-06 09:12:26	announced

10.1073/PNAS.2425622122;

submitter keyword: human cytomegalovirus

virion

quantitative proteomics

humoral immunity

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

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PRIDE project URI

• PRIDE
  1. PXD065223
     1. Label: PRIDE project
     2. Name: Virion Proteomics of Genetically Intact HCMV Reveals a Novel Regulator of Envelope Glycoprotein Composition that Protects Against Humoral Immunity