PXD068971-1

PXD068971 is an original dataset announced via ProteomeXchange.

Title	Myosin-9 is required for lysosome-mediated nonlytic reovirus egress
Description	Mammalian orthoreoviruses (reoviruses) are nonenveloped, double-stranded RNA viruses that assemble progeny particles in cytoplasmic viral factories (VFs) and exit some types of cells using a nonlytic release mechanism. In human brain microvascular endothelial cells (HBMECs), progeny reovirus virions are selectively sorted from VFs into sorting organelles (SOs), which are derived from lysosomes. Smaller membranous carriers (MCs) bud from SOs and transport progeny virions to the plasma membrane where they are released nonlytically by fusion of MCs with the plasma membrane. To discover cellular factors required for lysosomal modification and nonlytic egress, we used mass spectrometry to identify proteins associated with lysosomes purified from uninfected and reovirus-infected HBMECs as well as virions purified from HBMECs and L929 cells, which differ in the pathways used by reovirus for egress. Network analysis of the proteomic results from HBMECs yielded an enrichment of cytoskeletal proteins centered on myosin-9. Using siRNA gene-silencing of myosin-9, pharmacological inhibition of myosin-9, super-resolution light microscopy, electron microscopy, and three-dimensional electron tomography, we found that myosin-9 acts at late stages of reovirus replication to promote viral egress. Myosin-9 associates with actin filaments attached to mature virions and mediates nonlytic egress of viral progeny from HBMECs. Our findings provide insights into the role of myosin-9 in the intracellular lysosome-mediated reovirus egress pathway and illuminate a new potential therapeutic target for viruses that use this nonlytic egress pathway.
HostingRepository	PRIDE
AnnounceDate	2025-10-10
AnnouncementXML	Submission_2025-10-10_01:48:18.232.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD068971
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sergio Ciordia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Orthoreovirus; NCBI TaxID: NEWT:10882;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-29 12:21:45	ID requested
⏵ 1	2025-10-10 01:48:18	announced

10.1371/JOURNAL.PPAT.1013597;

10.6019/PXD068971;

submitter keyword: Reovirus

virus egress

myosin-9

proteomics

imaging

Cristina Risco Ortiz
contact affiliation	Centro Nacional de Biotecnología (CNB-CSIC)
contact email	crisco@cnb.csic.es
lab head
Sergio Ciordia
contact affiliation	Spanish National Center for Biotechnology
contact email	sciordia@cnb.csic.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD068971
     1. Label: PRIDE project
     2. Name: Myosin-9 is required for lysosome-mediated nonlytic reovirus egress