By Dr Rubaiyea Farruke, Research Officer in Professor Patrick Reading’s laboratory and Dr Jessie Jie-Youen Chang, Research Officer in Professor Lachlan Coin’s laboratory, both at the Doherty Institute
Did you know ferrets play a key role in the fight against influenza? In fact, they are considered the ‘gold standard’ animal model for studying influenza viruses. That’s because their respiratory system behaves much like that of humans.
Yet, despite relying on them for decades, we still know surprisingly little about how their immune system actually responds to influenza infections or antiviral agents like interferons, which are proteins produced by the body to fight infections. This knowledge gap makes it harder to apply findings from ferret studies directly to humans.
Our research set out to close that gap. Using long-read RNA sequencing, a cutting-edge technology that provides a complete picture of gene activity, we mapped the ferret’s genetic response to two key triggers: interferon treatment and influenza.
Unlike traditional methods, this technology allows us to uncover not only which genes switch on during infection or treatment, but also new gene variants and hidden features that were previously invisible.
The results were striking. First, ferrets activate many of the same antiviral genes as humans, during either infection or interferon treatment. We also discovered more than 1,000 potentially new genes in ferrets, significantly expanding the ferret genetic map.
Intriguingly, during interferon treatment we saw changes in the length of structures called poly(A) tails, which help control RNA stability. This suggests that ferrets may use RNA tail length to regulate their antiviral defences.
Additionally, we even detected unusual hybrid RNA molecules, with some parts belonging to one gene and another belonging to another, within a family of antiviral genes called IFITMs, hinting at new ways ferrets may fine-tune their immune response.
Our findings represent one of the first comprehensive looks at the ferret’s early immune response using long-read sequencing. By improving the genetic blueprint for ferrets and our understanding of their immune system, our work will help researchers better interpret influenza studies and test vaccines or treatments more effectively.
This research opens the door to exploring how these newly discovered genes and RNA features influence infection, knowledge that could ultimately help us better predict and control human influenza outbreaks.
More updates and news from the Doherty Institute
Public Health
