PXD046941

PXD046941 is an original dataset announced via ProteomeXchange.

Title	Landscape of protein-protein-interactions during hepatitis C virus assembly and release
Description	Assembly of infectious hepatitis C virus (HCV) particles requires multiple cellular proteins including for instance apolipoprotein E (ApoE). To describe these protein-protein-interactions, we performed an affinity purification mass spectrometry screen (AP-MS) of HCV infected cells. We used functional viral constructs with epitope-tagged envelope protein 2 (E2), protein (p)7 or nonstructural protein 4B (NS4B), as well as cells expressing a tagged variant of ApoE. We also evaluated assembly stage-dependent remodeling of protein complexes by using viral mutants carrying point mutations abrogating particle production at distinct steps of the HCV particle production cascade. Detected were five ApoE binding proteins, 12 p7 binders, seven primary E2-interactors and 24 proteins interacting with NS4B. Cell-derived PREB, STT3B, SPCS2 as well as viral NS2 interacted with both p7 and E2. Only GTF3C3 interacted with E2 and NS4B, highlighting that HCV assembly and replication complexes exhibit largely distinct interactomes. An HCV core protein mutation, preventing core protein decoration of lipid droplets, profoundly altered the E2 interactome. In cells replicating this mutant, E2 interactions with HSPA5, STT3A/B, RAD23A/B and ZNF860 were significantly enhanced, suggesting that E2 protein interactions partly depend on core protein functions. Bioinformatic and functional studies including STRING network analyses, RNA interference, and ectopic expression support a role of Rad23A and Rad23B in facilitating HCV infectious virus production. Both Rad23A and Rad23B are involved in the endoplasmic reticulum (ER)-associated protein degradation (ERAD). Collectively, our results provide a map of host proteins interacting with HCV assembly proteins and they give evidence for the involvement of ER protein folding machineries and the ERAD pathway in the late stages of the HCV replication cycle.
HostingRepository	PRIDE
AnnounceDate	2023-12-18
AnnouncementXML	Submission_2023-12-18_09:22:44.456.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-14 03:18:27	ID requested
⏵ 1	2023-12-18 09:22:44	announced

Dataset with its publication pending

submitter keyword: virus host interaction, AP-MS, hepatitis C virus, virus assembly,HCV

Felix Meissner
contact affiliation	Institute of Innate Immunity University Hospital Bonn
contact email	felix.meissner@uni-bonn.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
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/2023/12/PXD046941

PRIDE project URI

• PRIDE
  1. PXD046941
     1. Label: PRIDE project
     2. Name: Landscape of protein-protein-interactions during hepatitis C virus assembly and release