2026-08-10T01:37:26Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/254452025-12-18T12:56:28Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_16938col_20.500.12105_16982col_20.500.12105_25179
Repisalud
author
López-Ayllón, Blanca D
author
Marin, Silvia
author
Fariñas Fernández, Marco
author
García-García, Tránsito
author
Fernández-Rodríguez, Raúl
author
de Lucas-Rius, Ana
author
Redondo, Natalia
author
Mendoza-García, Laura
author
Foguet, Carles
author
Grigas, Juozas
author
Calvet, Alba
author
Villalba, José Manuel
author
Rodríguez, María Josefa
author
Megías, Diego
author
Mandracchia, Biagio
author
Luque, Daniel
author
Lozano, Juan José
author
Calvo, Cristina
author
Merino Herrán, Unai
author
Thomson, Timothy M
author
Garrido, Juan J
author
Cascante, Marta
author
Montoya, Maria
author
López-Ayllón, Blanca D
author
Marin, Silvia
author
Fariñas Fernández, Marco
author
García-García, Tránsito
author
Fernández-Rodríguez, Raúl
author
de Lucas-Rius, Ana
author
Redondo, Natalia
author
Mendoza-García, Laura
author
Foguet, Carles
author
Grigas, Juozas
author
Calvet, Alba
author
Villalba, José Manuel
author
Megías, Diego
author
Mandracchia, Biagio
author
Luque, Daniel
author
Lozano, Juan José
author
Calvo, Cristina
author
Merino Herrán, Unai
author
Thomson, Timothy M
author
Garrido, Juan J
author
Cascante, Marta
author
Montoya, María
funder
Unión Europea. Comisión Europea. NextGenerationEU
funder
Consejo Superior de Investigaciones Científicas (España)
funder
Regional Government of Andalusia (España)
funder
Ministerio de Ciencia (España)
funder
Agència de Gestió d´Ajuts Universitaris i de Recerca (AGAUR)
funder
Institució Catalana de Recerca i Estudis Avançats
funder
Instituto de Salud Carlos III
funder
Agencia Estatal de Investigación (España)
2024-11-06T11:26:15Z
2024-11-06T11:26:15Z
2024-07
J Med Virol . 2024 Jul;96(7):e29752.
10.1002/jmv.29752
1096-9071
0146-6615
Journal of medical virology
38949191
https://hdl.handle.net/20.500.12105/25445
Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.
eng
ORF10
ORF3a
ORF9b
ORF9c
Genome‐scale metabolic modeling
Metabolomics
Mitochondria
Transcriptomics
Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10
research article
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