Scientists discover gene linked to the severity of respiratory viral infections
In a world-first discovery that could revolutionise patient care, researchers including Dr Brendan Chua & Prof Katherine Kedzierska, have identified a gene associated with whether patients hospitalised with respiratory viral infections recover rapidly or face life-threatening complications.
With respiratory viral infections posing significant health threats, researchers and clinicians have long grappled with the mystery of why some individuals succumb to severe infections while others recover unscathed.
In a study published in Cell, researchers from the Department of Microbiology & Immunology (DMI) at the Peter Doherty Institute for Infection and Immunity (Doherty Institute), revealed the critical role of a gene called OLAH in disease severity. Their findings show that highly elevated expression levels of OLAH were strongly associated with severe respiratory viral infections, while minimal OLAH expression was found in recovery and milder disease.
Dr Brendon Chua, a viral and translational immunologist in DMI at the Doherty Institute, guided the innovative research and is a co-senior author of the paper.
Our first ‘aha’ moment occurred during our analysis of patients hospitalised with A(H7N9) influenza, where we discovered a consistent association between high expression levels of OLAH and fatal outcomes. Patients who recovered exhibited very low OLAH expression throughout their hospital stay.
“Further investigation using animal models and cell cultures revealed that OLAH is pivotal in driving life-threatening inflammation associated with respiratory viruses. What’s interesting is that we all have this gene, but its expression varies during the early phases of a respiratory infection, which is why some of us recover faster while others experience severe complications," Dr Chua said.
The researchers found elevated levels of OLAH in patients severely infected with seasonal influenza virus, SARS-CoV-2, respiratory syncytial virus (RSV) and in children experiencing multi-system inflammatory syndrome, a condition associated with COVID-19, but not in mild cases.
Professor Katherine Kedzierska, Head of the Human T cell Laboratory in DMI at the Doherty Institute, has been leading this research since 2013, 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 Professor Kedzierska.
“Imagine if your doctor could predict whether your respiratory infection will become life-threatening or if you'll recover quickly? 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 personalised treatment strategies.”
The team is now working on developing OLAH-based diagnostic methods that can be deployed in clinics to screen hospitalised patients upon admission and differentiate between those who will recover and those who will face life-threatening outcomes.
Professor Kedzierska and her team will explore how OLAH can inform the development of therapeutic treatments for pathogens of pandemic potential, one of the foundational projects funded by the Cumming Global Centre for Pandemic Therapeutics. The Centre was established following a $250 million donation to the University of Melbourne by Mr Geoffrey Cumming – the largest philanthropic donation to medical research in Australia’s history.
In this research paper published in the journal Cell in August 2024, the analysis of human cohorts with mild and life-threatening respiratory viral diseases, and in mouse models by Jia et al. reveal how high expression of a gene for a host enzyme involved in fatty acid production, oleoyl-ACP-hydrolase (OLAH), drives severe and fatal disease outcomes. This image depicts an artist’s interpretation of how OLAH gene expression serves as a doorway that leads to different disease outcomes. A wall represented by a chromosome separates uninfected individuals in the brightly lit side of the door juxtaposed by those are infected in the dark side. An infected person passing through this door and illuminated with a silhouette of a virus will face two paths, either to recovery or life-threatening complications. (Art and design by Su Min Suh, SciStories LLC)
This article was originally published by the Doherty Institute on 13 August 2024.
The Doherty Institute is a joint venture between The University of Melbourne and The Royal Melbourne Hospital