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

Jia, X; Crawford, JC; Gebregzabher, D; Monson, EA; Mettelman, RC; Wan, Y; Ren, Y; Chou, J; Novak, T; McQuilten, HA; Clarke, M; Bachem, A; Foo, IJ; Fritzlar, S; Carrera Montoya, J; Trenerry, AM; Nie, S; Leeming, MG; Nguyen, THO; Kedzierski, L; Littler, DR; Kueh, A; Cardamone, T; Wong, CY; Hensen, L; Cabug, A; Laguna, JG; Agrawal, M; Flerlage, T; Boyd, DF; Van de Velde, LA; Habel, JR; Loh, L; Koay, HF; van de Sandt, CE; Konstantinov, IE; Berzins, SP; Flanagan, KL; Wakim, LM; Herold, MJ; Green, AM; Smallwood, HS; Rossjohn, J; Thwaites, RS; Chiu, C; Scott, NE; Mackenzie, JM; Bedoui, S; Reading, PC; Londrigan, SL; Helbig, KJ; Randolph, AG; Thomas, PG; Xu, J; Wang, Z; Chua, BY; Kedzierska, K

Author(s): Jia, X; Crawford, JC; Gebregzabher, D; Monson, EA; Mettelman, RC; Wan, Y; Ren, Y; Chou, J; Novak, T; McQuilten, HA; Clarke, M; Bachem, A; Foo, IJ; Fritzlar, S; Carrera Montoya, J; Trenerry, AM; Nie, S; Leeming, MG; Nguyen, THO; Kedzierski, L; Littler, DR; Kueh, A; Cardamone, T; Wong, CY; Hensen, L; Cabug, A; Laguna, JG; Agrawal, M; Flerlage, T; Boyd, DF; Van de Velde, LA; Habel, JR; Loh, L; Koay, HF; van de Sandt, CE; Konstantinov, IE; Berzins, SP; Flanagan, KL; Wakim, LM; Herold, MJ; Green, AM; Smallwood, HS; Rossjohn, J; Thwaites, RS; Chiu, C; Scott, NE; Mackenzie, JM; Bedoui, S; Reading, PC; Londrigan, SL; Helbig, KJ; Randolph, AG; Thomas, PG; Xu, J; Wang, Z; Chua, BY; Kedzierska, K;
Details: Publication Year 2024-08-06,Volume 187,Issue #17,Page 4586-4604 e20
Journal Title: Cell
Abstract: 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.
Publisher: Cell Press
Keywords: Mis-c; Olah; SARS-CoV-2 and RSV; fatal avian A/H7N9 influenza disease; influenza mouse model; life-threatening seasonal influenza; olah(−/−) mice; olah-driven macrophage-mediated disease severity; oleoyl-ACP hydrolase as key early driver of disease severity
Research Division(s): Blood Cells And Blood Cancer
PubMed ID: 39137778
Publisher's Version: https://doi.org/10.1016/j.cell.2024.07.026
Open Access at Publisher's Site: https://doi.org/10.1016/j.cell.2024.07.026
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: PIIS0092867424008006.pdf - (13.82MB, application/pdf)

Creation Date: 2024-08-23 02:54:16

Last Modified: 2024-09-02 11:01:44