PXD062217-1

PXD062217 is an original dataset announced via ProteomeXchange.

Title	HIV-1 signalling remodels nuclear pores to licence infection
Description	HIV-1 is readily-detected in resting CD4+ T-cells in vivo1-4. However, resting T-cells are highly-refractory to cell-free virus infection in vitro5-7 and require mitogenic activation to become permissive. This paradox raises the fundamental question of what makes a T-cell permissive for HIV-1. Here we address this and show that HIV-1 capsid nuclear import at the nuclear pore complex (NPC) is a bottleneck to resting T-cell infection, but that HIV-1 overcomes this by triggering receptor-mediated signalling during cell-cell spread to drive nuclear import and licence infection. Coupling viral and cellular assays with super-resolution imaging we show that contact between HIV-1 infected and uninfected T-cells triggers CD4-Lck signalling that activates CDK1, independent of cell-cycle entry, phosphorylating nucleoporins and priming the NPC to promote HIV-1 nuclear import. Critically, cell-cell contact also accelerates nuclear import in activated T-cells, providing a new paradigm for why cell-cell spread dominates infection. By contrast, HIV-1 virions do not trigger this response, explaining why resting T-cells cannot be efficiently infected by cell-free virus. We propose that HIV-1 has evolved to activate CD4 signalling during cell-cell spread to regulate infection at the step of the NPC, thereby bypassing the need for T-cell activation and offering an explanation for how resting T-cells can be infected in vivo.
HostingRepository	PRIDE
AnnounceDate	2026-05-01
AnnouncementXML	Submission_2026-05-01_06:10:07.511.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	riccardo zenezini chiozzi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-25 09:25:28	ID requested
⏵ 1	2026-05-01 06:10:08	announced

10.1038/S41586-026-10453-3;

submitter keyword: HIV, CDK1, Nucleoporin, T-cell, CD4, NPC

Thalassinos, Konstantinos
contact affiliation	Professor of Mass Spectrometry, Structural & Molecular Biology, UCL
contact email	k.thalassinos@ucl.ac.uk
lab head
riccardo zenezini chiozzi
contact affiliation	UCL
contact email	r.chiozzi@ucl.ac.uk
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/2026/05/PXD062217

PRIDE project URI

• PRIDE
  1. PXD062217
     1. Label: PRIDE project
     2. Name: HIV-1 signalling remodels nuclear pores to licence infection