Study reveals oleoyl-ACP-hydrolase underpins lethal respiratory viral disease

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Study reveals oleoyl-ACP-hydrolase underpins lethal respiratory viral disease

Potential impact on human health and disease 

Co-corresponding and senior author Katherine Kedzierska, PhD, Head of the Human T cell Laboratory at the Doherty Institute, highlighted the research’s significance in advancing our understanding of respiratory viruses and its potential far-reaching impact on patients’ health. 

“We’re really excited about the potential of the OLAH gene to serve as a universal indicator of disease severity across different respiratory infections,” said Kedzierska. 

“Imagine if your doctor could predict whether your respiratory infection will become life-threatening or if you’ll recover rapidly? Our findings suggest that OLAH expression levels could be used as a cutting-edge tool in assessing patients’ prognosis, empowering clinicians with crucial insights for early risk assessment and personalized treatment strategies,” she added. 

In addition to defining the role of OLAH in severe respiratory viral disease, the understanding that OLAH expression begins early in severe disease may make it useful as a biomarker to determine if patients need more intense initial treatment. Also, in mouse models, supplementing oleic acid increased influenza replication in macrophages and their inflammatory potential. This may mean that modulating oleic acid levels can be explored as a potential therapeutic approach to disease.  

“It took years of working closely with basic scientists and clinicians, from across the world, all studying different infections and diseases, for OLAH’s important role in immune response to come to light. This is just the beginning of our exploration of OLAH; there is a lot more work to be done in infectious disease and other potential applications,” Crawford said.  

Authors and funding 

The study’s other co-first author is Xiaoxiao Jia, Doherty Institute. The study’s other co-corresponding authors are Zhongfang Wang University of Melbourne and Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, and Brendon Chua, Doherty Institute.  

The study’s other authors include Deborah Gebregzabher, Hayley McQuilten, Michele Clarke, Annabell Bachem, Isabelle Foo, Svenja Fritzlar, Julio Carrera Montoya, Alice Trenerry, Shuai Nie, Michael Leeming, Thi H O Nguyen, Lukasz Kedzierski, Andrew Kueh, Tina Cardamone, Chinn Yi Wong, Luca Hensen, Aira Cabug, Jennifer Habel, Liyen Loh, Hui-Fern Koay, Carolien E van de Sandt, Linda Wakim, Marco Herold, Igor Konstantinov, Nichollas Scott, Jason Mackenzie, Sammy Bedoui, Patrick Reading, and Sarah Londrigan, University of Melbourne; Ebony Monson, La Trobe University; Yanmin Wan, Shanghai Medical College; Yanqin Ren, Fudan University; Janet Chou, and Tanya Novak, Boston Children’s Hospital; Dene Littler, Monash University; Jamie Gomez Laguna, University of Cordoba; Heather Smallwood, and Mona Agrawal, University of Tennessee Health Science Center; David Boyd, University of California, Santa Cruz; Stuart Berzins, University of Melbourne and Federation University Australia; Katie Flanagan, University of Tasmania; Jamie Rossjohn, Monash University and Cardiff University School of Medicine; Ryan Thwaites, and Christopher Chiu, Imperial College London; Adrienne Randolph, Boston Children’s Hospital and the Center for Influenza Disease and Emergence Response; and Robert Mettelman, Tim Flerlage, Lee-Ann Van de Velde, Amanda Green, and Karla Helbig of St. Jude

The study was supported by the National Health and Medical Research Council of Australia (#1173871, #1194036, and #2001346), China Scholarship Council-UoM Joint Scholarship, the National Institutes of Health (R01AI136514, U01AI150747), and ALSAC, the fundraising and awareness organization of St. Jude


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