tetano
Editor, Senior Moderator
Cell
. 2024 Aug 6:S0092-8674(24)00800-6.
doi: 10.1016/j.cell.2024.07.026. Online ahead of print. High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases
Xiaoxiao Jia[SUP] 1 [/SUP], Jeremy Chase Crawford[SUP] 2 [/SUP], Deborah Gebregzabher[SUP] 1 [/SUP], Ebony A Monson[SUP] 3 [/SUP], Robert C Mettelman[SUP] 4 [/SUP], Yanmin Wan[SUP] 5 [/SUP], Yanqin Ren[SUP] 6 [/SUP], Janet Chou[SUP] 7 [/SUP], Tanya Novak[SUP] 8 [/SUP], Hayley A McQuilten[SUP] 1 [/SUP], Michele Clarke[SUP] 1 [/SUP], Annabell Bachem[SUP] 1 [/SUP], Isabelle J Foo[SUP] 1 [/SUP], Svenja Fritzlar[SUP] 1 [/SUP], Julio Carrera Montoya[SUP] 1 [/SUP], Alice M Trenerry[SUP] 1 [/SUP], Shuai Nie[SUP] 9 [/SUP], Michael G Leeming[SUP] 9 [/SUP], Thi H O Nguyen[SUP] 1 [/SUP], Lukasz Kedzierski[SUP] 1 [/SUP], Dene R Littler[SUP] 10 [/SUP], Andrew Kueh[SUP] 11 [/SUP], Tina Cardamone[SUP] 12 [/SUP], Chinn Yi Wong[SUP] 1 [/SUP], Luca Hensen[SUP] 1 [/SUP], Aira Cabug[SUP] 1 [/SUP], Jaime Gómez Laguna[SUP] 13 [/SUP], Mona Agrawal[SUP] 14 [/SUP], Tim Flerlage[SUP] 15 [/SUP], David F Boyd[SUP] 16 [/SUP], Lee-Ann Van de Velde[SUP] 4 [/SUP], Jennifer R Habel[SUP] 1 [/SUP], Liyen Loh[SUP] 1 [/SUP], Hui-Fern Koay[SUP] 1 [/SUP], Carolien E van de Sandt[SUP] 1 [/SUP], Igor E Konstantinov[SUP] 17 [/SUP], Stuart P Berzins[SUP] 18 [/SUP], Katie L Flanagan[SUP] 19 [/SUP], Linda M Wakim[SUP] 1 [/SUP], Marco J Herold[SUP] 11 [/SUP], Amanda M Green[SUP] 20 [/SUP], Heather S Smallwood[SUP] 14 [/SUP], Jamie Rossjohn[SUP] 21 [/SUP], Ryan S Thwaites[SUP] 22 [/SUP], Christopher Chiu[SUP] 23 [/SUP], Nichollas E Scott[SUP] 1 [/SUP], Jason M Mackenzie[SUP] 1 [/SUP], Sammy Bedoui[SUP] 1 [/SUP], Patrick C Reading[SUP] 1 [/SUP], Sarah L Londrigan[SUP] 1 [/SUP], Karla J Helbig[SUP] 3 [/SUP], Adrienne G Randolph[SUP] 24 [/SUP], Paul G Thomas[SUP] 25 [/SUP], Jianqing Xu[SUP] 5 [/SUP], Zhongfang Wang[SUP] 26 [/SUP], Brendon Y Chua[SUP] 27 [/SUP], Katherine Kedzierska[SUP] 28 [/SUP]
Affiliations
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[SUP]-/-[/SUP] 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.
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.
. 2024 Aug 6:S0092-8674(24)00800-6.
doi: 10.1016/j.cell.2024.07.026. Online ahead of print. High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases
Xiaoxiao Jia[SUP] 1 [/SUP], Jeremy Chase Crawford[SUP] 2 [/SUP], Deborah Gebregzabher[SUP] 1 [/SUP], Ebony A Monson[SUP] 3 [/SUP], Robert C Mettelman[SUP] 4 [/SUP], Yanmin Wan[SUP] 5 [/SUP], Yanqin Ren[SUP] 6 [/SUP], Janet Chou[SUP] 7 [/SUP], Tanya Novak[SUP] 8 [/SUP], Hayley A McQuilten[SUP] 1 [/SUP], Michele Clarke[SUP] 1 [/SUP], Annabell Bachem[SUP] 1 [/SUP], Isabelle J Foo[SUP] 1 [/SUP], Svenja Fritzlar[SUP] 1 [/SUP], Julio Carrera Montoya[SUP] 1 [/SUP], Alice M Trenerry[SUP] 1 [/SUP], Shuai Nie[SUP] 9 [/SUP], Michael G Leeming[SUP] 9 [/SUP], Thi H O Nguyen[SUP] 1 [/SUP], Lukasz Kedzierski[SUP] 1 [/SUP], Dene R Littler[SUP] 10 [/SUP], Andrew Kueh[SUP] 11 [/SUP], Tina Cardamone[SUP] 12 [/SUP], Chinn Yi Wong[SUP] 1 [/SUP], Luca Hensen[SUP] 1 [/SUP], Aira Cabug[SUP] 1 [/SUP], Jaime Gómez Laguna[SUP] 13 [/SUP], Mona Agrawal[SUP] 14 [/SUP], Tim Flerlage[SUP] 15 [/SUP], David F Boyd[SUP] 16 [/SUP], Lee-Ann Van de Velde[SUP] 4 [/SUP], Jennifer R Habel[SUP] 1 [/SUP], Liyen Loh[SUP] 1 [/SUP], Hui-Fern Koay[SUP] 1 [/SUP], Carolien E van de Sandt[SUP] 1 [/SUP], Igor E Konstantinov[SUP] 17 [/SUP], Stuart P Berzins[SUP] 18 [/SUP], Katie L Flanagan[SUP] 19 [/SUP], Linda M Wakim[SUP] 1 [/SUP], Marco J Herold[SUP] 11 [/SUP], Amanda M Green[SUP] 20 [/SUP], Heather S Smallwood[SUP] 14 [/SUP], Jamie Rossjohn[SUP] 21 [/SUP], Ryan S Thwaites[SUP] 22 [/SUP], Christopher Chiu[SUP] 23 [/SUP], Nichollas E Scott[SUP] 1 [/SUP], Jason M Mackenzie[SUP] 1 [/SUP], Sammy Bedoui[SUP] 1 [/SUP], Patrick C Reading[SUP] 1 [/SUP], Sarah L Londrigan[SUP] 1 [/SUP], Karla J Helbig[SUP] 3 [/SUP], Adrienne G Randolph[SUP] 24 [/SUP], Paul G Thomas[SUP] 25 [/SUP], Jianqing Xu[SUP] 5 [/SUP], Zhongfang Wang[SUP] 26 [/SUP], Brendon Y Chua[SUP] 27 [/SUP], Katherine Kedzierska[SUP] 28 [/SUP]
Affiliations
- PMID: 39137778
- DOI: 10.1016/j.cell.2024.07.026
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[SUP]-/-[/SUP] 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.
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.