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PXD070575

PXD070575 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomics of A549 and A549 cells transducted with ORF7a SARS-CoV-2 accessory protein
DescriptionSARS-CoV-2 reprograms host metabolism to facilitate immune evasion and viral replication. While infection is known to impair mitochondrial function and enhance glycolysis, the role of viral accessory proteins in these alterations remains unclear. Here, we investigate the metabolic impact of the accessory protein ORF7a. Using lentiviral transduction, we expressed ORF7a in human lung epithelial (A549) and monocytic (THP1) cells. Integrated transcriptomic, proteomic, and metabolomic analyses in A549 cells revealed profound dysregulation of glucose and lipid metabolism. ORF7a impaired oxidative phosphorylation, as shown by reduced basal and maximal respiration, mitochondrial depolarization, and elevated reactive oxygen species. ORF7a induced upregulation of pyruvate dehydrogenase kinase 4 (PDK4) and increased phosphorylation of the pyruvate dehydrogenase complex (PDHC), leading to impaired pyruvate oxidation. However, pharmacological inhibition of PDK4 with dichloroacetate failed to rescue mitochondrial respiration, suggesting additional dysfunction. Enzymatic assays confirmed reduced complex I activity, pointing to direct impairment of the electron transport chain. Our findings demonstrate that ORF7a orchestrates a multifaceted metabolic reprogramming involving PDK4-dependent PDHC inhibition and complex I dysfunction. These results highlight ORF7a as a key modulator of host metabolism and underscore mitochondrial pathways as potential therapeutic targets in COVID-19.
HostingRepositoryPRIDE
AnnounceDate2026-07-08
AnnouncementXMLSubmission_2026-07-08_06:31:56.010.xml
DigitalObjectIdentifierhttps://doi.org/10.6019/PXD070575
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterRaúl Fernández Rodríguez
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-11-10 23:41:07ID requested
12026-07-08 06:31:56announced
Publication List
10.6019/PXD070575;
Keyword List
submitter keyword: SARS-CoV-2
accessory proteins
ORF7a
COVID-19
Contact List
Tránsito García García
contact affiliationDepartment of Genetics, Immunogenomics and Molecular Pathogenesis Group, UIC Zoonoses and Emergent Diseases ENZOEM, University of Córdoba, Córdoba, Spain
contact emailb52gagat@uco.es
lab head
Raúl Fernández Rodríguez
contact affiliationDepartment of Genetics, Immunogenomics and Molecular Pathogenesis Group, UIC Zoonoses and Emergent Diseases ENZOEM, University of Córdoba, Córdoba, Spain.
contact emailb42feror@uco.es
dataset submitter
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