Gammaherpesvirus Found to Drive Lasting Lung Scarring Through Immune Cell Cross-Talk
Nikhil Prasad Fact checked by:Thailand Medical News Team Jul 28, 2026 1 hour, 4 minutes ago
Medical News: Gammaherpesviruses are a subgroup of the herpesvirus family that establish lifelong infections after entering the body. Unlike viruses that disappear after recovery, gammaherpesviruses remain dormant inside immune cells and can subtly influence the immune system for years. In humans, the best-known gammaherpesvirus is the Epstein-Barr virus (EBV), which infects more than 90 percent of the world's population. Although most infections remain symptom-free after the initial illness, scientists have increasingly suspected that these viruses may contribute to chronic diseases, including pulmonary fibrosis. Now, researchers from the University of Liège, GIGA Institute, University Hospital CHU of Liège, and WELBIO in Belgium, Maastricht University Medical Centre+ in the Netherlands, and RWTH Aachen University in Germany have uncovered a previously unknown mechanism showing how gammaherpesvirus infection can prevent damaged lungs from healing properly.
Scientists discovered that gammaherpesvirus infection leaves lasting immune changes that fuel persistent
lung scarring through harmful communication between T cells and fibroblasts.
Gammaherpesvirus Leaves Behind Long-Lasting Immune Changes
Pulmonary fibrosis is a serious disease in which healthy lung tissue is gradually replaced by scar tissue, making breathing increasingly difficult. While genetics, environmental exposures and aging all contribute to the disease, scientists have struggled to understand why some patients continue to develop worsening fibrosis long after an injury has occurred.
Using mice infected with Murid herpesvirus-4 (MuHV-4), the mouse equivalent of human Epstein-Barr virus, researchers found that prior gammaherpesvirus infection significantly impaired the lungs' ability to recover after injury caused by bleomycin.
Interestingly, the worsening fibrosis was not caused by renewed viral activity. Instead, the virus appeared to permanently reshape the immune system, leaving behind changes that continued to promote scarring weeks after the infection itself had entered its dormant phase.
Immune Cells and Fibroblasts Form a Dangerous Partnership
This
Medical News report reveals that the researchers identified an unexpected interaction between immune cells known as CD8+ T cells and lung fibroblasts, the cells responsible for producing connective tissue during repair.
Following gammaherpesvirus infection, large numbers of activated memory CD8+ T cells accumulated inside the lungs and produced high amounts of the inflammatory signaling molecule interferon-gamma (IFN-γ). In response, nearby fibroblasts dramatically increased production of PD-L1 while the activated T cells displayed elevated levels of PD-1.
Using sophisticated multiplex spectral imaging, the researchers observed that these PD-1-positive T cells clustered directly beside PD-L1-positive fibroblasts inside heavily scarred regions of the lungs. Wherever these cellular clusters appeared, collagen deposits were substan
tially greater, strongly suggesting that this communication between the two cell types was actively maintaining fibrosis rather than allowing normal healing.
Blocking PD-1 Signaling Reduced Persistent Fibrosis
One of the study's most important discoveries came when scientists interrupted the PD-1/PD-L1 signaling pathway after fibrosis had already developed.
Animals treated with PD-1-blocking antibodies experienced significantly better resolution of lung scarring. Measurements showed lower collagen accumulation, reduced expression of collagen-producing genes, and an overall improvement in lung tissue recovery.
The researchers also examined alveolar macrophages, immune cells previously believed to play a major role in fibrosis. Although these cells were altered following gammaherpesvirus infection, they did not display stronger profibrotic behavior. Instead, the evidence consistently pointed toward activated memory CD8+ T cells as the major drivers of persistent fibrosis.
Human Experiments Confirm Similar Effects
To determine whether these findings could be relevant to people, the investigators performed laboratory experiments using human lung fibroblasts together with CD8+ T cells obtained from EBV-positive and EBV-negative volunteers.
Activated CD8+ T cells from EBV-positive donors stimulated fibroblasts to produce significantly higher levels of collagen-related and profibrotic genes. When PD-L1 was blocked, this harmful response disappeared. In contrast, CD8+ T cells from EBV-negative donors failed to trigger the same profibrotic activity, providing strong evidence that prior gammaherpesvirus infection can leave behind long-term immune changes capable of driving excessive tissue scarring.
Conclusion
The study provides compelling evidence that gammaherpesvirus infection may contribute to chronic lung fibrosis by permanently altering immune memory rather than through ongoing viral replication. By identifying the harmful interaction between PD-1-positive CD8+ T cells and PD-L1-positive fibroblasts, the research opens the door to potential therapies that target this immune checkpoint pathway to promote healing and slow or even reverse persistent lung scarring.
The study findings were published in the peer reviewed journal: Mucosal Immunology.
https://www.sciencedirect.com/science/article/pii/S1933021926000905
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