Proteomics of A549 and A549 cells transducted with ORF7a SARS-CoV-2 accessory protein

ABSTRACT: SARS-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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell

SUBMITTER: Raúl Fernández Rodríguez  

LAB HEAD: Tránsito García García

PROVIDER: PXD070575 | Pride | 2026-07-08

REPOSITORIES: Pride