Gene linked to life-threatening respiratory viral infections

Doctors may soon be able to predict whether your influenza infection will become life-threatening, or if you’ll recover quickly.

Scientists have identified a gene associated with whether patients hospitalised with respiratory viral infections will experience mild disease or life-threatening complications.

Scientists have identified a gene associated with whether patients hospitalised with respiratory viral infections experience mild disease or life-threatening complications.

According to the new study published in Cell, expression levels of the gene, OLAH, is critical in determining disease severity.

The University of Melbourne’s Dr Brendon Chua, a viral and translational immunologist at the Doherty Institute for Infection and Immunity and co-senior author of the paper, says: “Our first ‘aha’ moment occurred during our analysis of patients hospitalised with A(H7N9) [avian] influenza, where we discovered a consistent association between high expression levels of OLAH and fatal outcomes.

“Conversely, patients who recovered exhibited very low OLAH expression throughout their hospital stay.

Patients severely infected with seasonal influenza virus, SARS-CoV-2, respiratory syncytial virus (RSV) and children experiencing multisystem inflammatory syndrome, a rare but serious complication of COVID-19, also show elevated levels of OLAH expression.

The OLAH gene encodes an enzyme, oleoyl-acyl-carrier-protein hydrolase (OLAH), which mediates the production of a fatty acid. Higher expression of the gene results in higher levels of fatty acids, which exacerbates viral infections.

“Further investigation using animal models and cell cultures revealed that OLAH is pivotal in driving life-threatening inflammation associated with respiratory viruses,” says Chua.

“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.”

The research team is now working to develop OLAH-based diagnostic methods to screen hospitalised patients. They are also exploring how OLAH can inform the development of therapeutic treatments for viral pathogens.

The University of Melbourne’s Professor Katherine Kedzierska, head of the Human T cell Laboratory at the Doherty Institute and co-senior author of the paper, says: “We’re really excited about the potential of the OLAH gene to serve as a universal indicator of disease severity across different respiratory infections.

“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.”