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Publication : High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases.

First Author  Jia X Year  2024
Journal  Cell Volume  187
Issue  17 Pages  4586-4604.e20
PubMed ID  39137778 Mgi Jnum  J:353571
Mgi Id  MGI:7716298 Doi  10.1016/j.cell.2024.07.026
Citation  Jia X, et al. (2024) High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases. Cell 187(17):4586-4604.e20
abstractText  Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah(-/-) mice, lethal influenza infection led to survival and mild disease as well as reduced lung viral loads, tissue damage, infection-driven pulmonary cell infiltration, and inflammation. This was underpinned by differential lipid droplet dynamics as well as reduced viral replication and virus-induced inflammation in macrophages. Supplementation of oleic acid, the main product of OLAH, increased influenza replication in macrophages and their inflammatory potential. Our findings define how the expression of OLAH drives life-threatening viral disease.
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