Researchers have discovered a new method to boost the body’s natural ability to fight respiratory viruses, including respiratory syncytial virus (RSV), one of the leading causes of severe lung infections worldwide.
An international team, involving scientists from University of Liverpool, The Chinese Academy of Medical Sciences Oxford Institute (COI), and the University of Zurich, found that activating a key oxygen-sensing pathway in cells can significantly limit viral replication and improve antiviral immunity.
Reprogramming the immune response
The hypoxia-inducible factor (HIF) pathway helps cells respond to low oxygen. The researchers activated the HIF pathway using Daprodustat, a drug already approved for clinical use. This treatment enhanced the body’s innate immune response, the first line of defence against viral infection, by boosting the expression of antiviral genes and interferon signalling.
Crucially, the study revealed that this effect depends on the body’s ability to detect viral genetic material. When key viral sensing pathways were blocked, the protective effect of HIF activation was lost, highlighting the importance of early immune detection.
Making viruses more visible
The team also uncovered a previously unrecognised mechanism by which HIF activation improves immune defence. Central to this process is a chemical modification of RNA known as N6-methyladenosine (m⁶A), which is commonly added to viral RNA and can help viruses evade immune recognition. The researchers found that activation of the HIF pathway promotes ‘eraser proteins’ that remove m⁶A modifications on RSV RNA. This reduction in m⁶A modifications resulted in the viral genome being more readily detectable by cellular RNA sensors, which are responsible for triggering antiviral interferon responses.
Dr Peter Wing, COI said: “By stripping away a layer of molecular camouflage, HIF activation enhances the ability of host cells to recognise the virus and mount a rapid immune response. This discovery highlights a new link between cellular metabolism, RNA modification, and antiviral defence.”
Professor James Stewart, University of Liverpool commented: “Respiratory syncytial virus remains a leading cause of hospitalisation worldwide, particularly in young children, with limited treatment options available. Our findings suggest that repurposing existing drugs that target the HIF pathway could offer a new therapeutic approach. The study provides fresh insight into how oxygen-sensing pathways interact with antiviral immunity and opens new avenues for the development of treatments against respiratory viral infections.”
The paper, ‘Hypoxia inducible factors regulate Pneumovirus replication by enhancing innate immune sensing’, is published in Proceedings of the National Academy of Sciences (PNAS) (DOI: 10.1073/pnas.2506647123).
Infection resilience
Infectious diseases know no borders. At the University of Liverpool our Infection resilience frontier addresses urgent global and national challenges in infection resilience, delivering scientific breakthroughs and practical solutions. From shaping UK government policy to advising global health organisations, our experts help steer the world towards better preparedness, faster response, and stronger defences.