Does early-life respiratory syncytial virus infection induce epigenetic changes that promote asthma development?

Respiratory viral infections in early life are strongly associated with the development of childhood asthma, although the mechanisms linking infection to long-term respiratory outcomes remain unclear. It is not yet established whether viral infections directly cause persistent airway damage or instead unmask an underlying host susceptibility. Increasing evidence suggests that epigenetic mechanisms, particularly DNA methylation, may act as a biological interface connecting environmental exposures with immune and respiratory development. Epigenome-wide association studies have identified consistent DNA methylation signatures associated with childhood asthma, suggesting that altered immune programming may precede clinical disease rather than simply reflecting established inflammation. Our recent work in children hospitalized with respiratory syncytial virus (RSV) infection provides additional insights into the role of the epigenome in shaping later respiratory sequelae. In a longitudinal study, DNA methylation profiles obtained during the acute phase of infection were associated with subsequent wheezing and asthma development. In this Perspective, we explore the hypothesis that early-life RSV infection may contribute to epigenetic changes that increase the risk of developing asthma later in life. By examining DNA methylation biomarkers previously associated with asthma in our cohort of RSV-infected children, we observed that individuals who later developed asthma showed more alterations in these biomarkers, predominantly hypomethylation patterns consistent with prior asthma studies. These proof-of-concept findings suggest that RSV infection may initiate asthma-related epigenetic mechanisms. Further longitudinal studies are needed to determine whether these changes reflect pre-existing susceptibility or infection-induced epigenetic remodeling, and to clarify their persistence and functional impact on immune and airway biology.