PXD070991-1

PXD070991 is an original dataset announced via ProteomeXchange.

Title	Pre-assembly of biomolecular condensate seeds drives RSV replication
Description	During infection many RNA viruses, including respiratory syncytial virus (RSV), form specialized biomolecular condensates, viral factories (VFs), where viral transcription and replication occur1-4. Paradoxically, high protein concentrations are typically required for condensate nucleation5, yet attaining sufficient protein levels in infection is thought to require VFs for viral transcription and replication. To uncover how viruses solve this paradox to establish VFs, we visualized early infection of RSV in real-time with single genomic viral ribonucleoprotein (vRNP) resolution. Our results reveal that VFs are nucleated from infecting vRNPs rather than de novo in the cytoplasm. VF nucleation further requires in-virion pre-assembly of viral protein-protein interaction networks on vRNPs to form ‘pre-replication centers’ (PRCs). PRCs are potent condensate nucleation seeds due to efficient recruitment and retention of viral proteins. The high affinity of PRCs also results in increased association of the viral polymerase and its co-factors, allowing efficient viral transcription even in the absence of VFs. Together, these activities create a feed-forward loop that drives rapid VF formation. Intriguingly, PRC assembly depends on in-virion viral protein levels and is highly heterogeneous among virions, explaining cell-to-cell heterogeneity in infection progression, and identifying heterogeneous virions as an important origin of infection heterogeneity. Together, our results show that in-virion pre-assembly of PRCs kick-starts viral condensate nucleation upon host-cell entry and explains cell-to-cell heterogeneity in RSV infection.
HostingRepository	PRIDE
AnnounceDate	2026-04-06
AnnouncementXML	Submission_2026-04-05_17:03:31.602.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD070991
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Yana Demyanenko
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-20 06:51:14	ID requested
⏵ 1	2026-04-05 17:03:32	announced

10.1038/s41586-025-10071-5;

10.6019/PXD070991;

Ratnayake D, Galloux M, Boersma S, Noerenberg M, Sizun C, Sacristan C, Sourimant J, Lakerveld AJ, Gelderloos AT, Apperloo L, Demyanenko Y, Baars MJD, Banerjee R, Dreier B, Furler S, Mazur NI, Bont LJ, Mohammed S, Pl, ü, ckthun A, É, l, é, ou, ë, t JF, Kops GJPL, Castello A, van Kasteren PB, Rameix-Welti MA, Tanenbaum ME, Pre-assembly of biomolecular condensate seeds drives RSV replication. Nature, 652(8108):189-200(2026) [pubmed]

submitter keyword: Ascend, Phospho-proteomics, Human, Immunoprecipitation, RSV

Marvin Tanenbaum
contact affiliation	Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, the Netherland Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Technische Universiteit Delft, Van der Maasweg 9, 2629 HZ Delft, the Netherlands.
contact email	m.tanenbaum@hubrecht.eu
lab head
Yana Demyanenko
contact affiliation	Rosalind Franklin Institute
contact email	yana.demyanenko@rfi.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/2026/04/PXD070991

PRIDE project URI

• PRIDE
  1. PXD070991
     1. Label: PRIDE project
     2. Name: Pre-assembly of biomolecular condensate seeds drives RSV replication