University of Manchester biologists have for the first time started to unpick the long-term biological changes associated with serious viral lung infections, such as flu and long-covid, in a study of mice.
Previously, little was known about the drivers of post-infection symptoms typically associated with severe viral infections, such as breathlessness and fatigue, but the study sheds light on what exactly might underpin these long-term effects.
"Serious viral infections like influenza and Sars-CoV-2 can cause long-term breathlessness and fatigue, though until now, the biological context to this has puzzled scientists," said co-author Prof Tracy Hussell from The University of Manchester:
The study, funded by Wellcome and published in the journal Mucosal Immunology, also explains how inflammation may lead to aging in the lungs.
The researchers found that following severe viral infection, a critical structure in the lung remains damaged, even after the symptoms and virus have both cleared.
The structure, known as the basement membrane, is a thin supportive layer of extracellular matrix that anchors and separates cells from underlying tissue
The basement membrane forms a barrier to line airspaces, support cells, and regulate fluid and cell movement.
For the study, the lungs of mice with influenza virus were analysed by proteomic mass spectrometry, to identify potential protein biomarkers compared to non-infected mice.
The study also used peptide location fingerprinting, a technique developed by Dr Eckersley's lab, which can identify damage across protein structures.
They found that basement membrane proteins had reduced abundance and harboured structural damage following recovery from infection.
That suggests post-viral damage is long-term, and that the membrane does not repair appropriately. The damage appeared patchy when observed histologically and resulted in leaky lungs.
As similar structural damage was also observed by the scientists in aged lungs of non-infected mice, they propose that long-term, age-related complications may be caused by repeated inflammation.
Dr Alex Eckersley, from the University of Manchester said: "We're very excited about our findings which reveal a new angle on why some viral infections have a long-term impact on lung health.
"Our study suggests that similar processes occur both when your lungs are exposed to a serious viral infection, and when you age.
"This means repeated viral infection could cause some people's lungs to age more quickly."
In many cases, the resolution of inflammation is incomplete, and the lung is thought to accumulate damage as a result over time.
By identifying evidence for this process, the researchers hope to have found a new area of interest in developing therapeutic targets for treating long-term post-viral symptoms.
He added: "By identifying these persistent basement membrane changes, we provide an entirely novel area to target with new medicines to treat complications arising from viral infection.
"By providing new therapeutic targets, and opportunities to broaden our understanding of how relevant biological structures might be being damaged or struggling to repair, we can better understand, research, and medicate post-viral symptoms."
Lung basement membranes are compositionally and structurally altered following resolution of influenza infection is published in Musocal Immunology . DOI: 10.1016/j.mucimm.2025.11.005
