Your browser doesn't support javascript.
loading
High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases.
Jia, Xiaoxiao; Crawford, Jeremy Chase; Gebregzabher, Deborah; Monson, Ebony A; Mettelman, Robert C; Wan, Yanmin; Ren, Yanqin; Chou, Janet; Novak, Tanya; McQuilten, Hayley A; Clarke, Michele; Bachem, Annabell; Foo, Isabelle J; Fritzlar, Svenja; Carrera Montoya, Julio; Trenerry, Alice M; Nie, Shuai; Leeming, Michael G; Nguyen, Thi H O; Kedzierski, Lukasz; Littler, Dene R; Kueh, Andrew; Cardamone, Tina; Wong, Chinn Yi; Hensen, Luca; Cabug, Aira; Laguna, Jaime Gómez; Agrawal, Mona; Flerlage, Tim; Boyd, David F; Van de Velde, Lee-Ann; Habel, Jennifer R; Loh, Liyen; Koay, Hui-Fern; van de Sandt, Carolien E; Konstantinov, Igor E; Berzins, Stuart P; Flanagan, Katie L; Wakim, Linda M; Herold, Marco J; Green, Amanda M; Smallwood, Heather S; Rossjohn, Jamie; Thwaites, Ryan S; Chiu, Christopher; Scott, Nichollas E; Mackenzie, Jason M; Bedoui, Sammy; Reading, Patrick C; Londrigan, Sarah L.
Afiliação
  • Jia X; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Crawford JC; Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Center for Infectious Diseases Research, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: jeremy.crawford@stjude.org.
  • Gebregzabher D; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Monson EA; Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia.
  • Mettelman RC; Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Wan Y; Shanghai Public Health Clinical Centre and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China.
  • Ren Y; Shanghai Public Health Clinical Centre, Fudan University, Shanghai 201508, China.
  • Chou J; Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Novak T; Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital and Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA.
  • McQuilten HA; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Clarke M; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Bachem A; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Foo IJ; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Fritzlar S; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Carrera Montoya J; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Trenerry AM; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Nie S; Melbourne Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3052, Australia.
  • Leeming MG; Melbourne Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3052, Australia.
  • Nguyen THO; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Kedzierski L; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Littler DR; Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
  • Kueh A; Walter Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bund
  • Cardamone T; Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC 3010, Australia.
  • Wong CY; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Hensen L; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Cabug A; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Laguna JG; Department of Anatomy and Comparative Pathology and Toxicology, Pathology and Immunology Group, University of Córdoba, International Excellence Agrifood Campus "CeiA3", 14014 Córdoba, Spain.
  • Agrawal M; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Flerlage T; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Boyd DF; Department of Molecular, Cell & Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Van de Velde LA; Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Habel JR; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Loh L; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Koay HF; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • van de Sandt CE; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Konstantinov IE; Department of Cardiothoracic Surgery, Royal Children's Hospital, University of Melbourne, Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine, Parkville, VIC 3052, Australia.
  • Berzins SP; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Institute of Innovation, Science and Sustainability, Federation University Australia, Ballarat, VIC 3353, Australia.
  • Flanagan KL; School of Health Sciences and School of Medicine, University of Tasmania, Launceston, TAS 7248, Australia; School of Health and Biomedical Science, RMIT University, Bundoora, VIC 3083, Australia; Tasmanian Vaccine Trial Centre, Clifford Craig Foundation, Launceston General Hospital, Launceston, TAS
  • Wakim LM; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Herold MJ; Walter Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bund
  • Green AM; Center for Infectious Diseases Research, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Smallwood HS; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • Rossjohn J; Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, UK.
  • Thwaites RS; National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
  • Chiu C; Department of Infectious Disease, Imperial College London, London, UK.
  • Scott NE; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Mackenzie JM; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Bedoui S; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Reading PC; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Londrigan SL; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
Cell ; 2024 Aug 06.
Article em En | MEDLINE | ID: mdl-39137778
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.
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Austrália
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Austrália