Potential for prolonged replication of common acute respiratory viruses in air-liquid interface cultures of primary human airway cells

This study demonstrates that most common respiratory viruses, excluding influenza and DNA viruses, can replicate and produce infectious progeny for an average of up to 100 days in air-liquid interface (ALI) cultures of primary human respiratory epithelial cells without obvious innate immune responses. These findings imply that extended viral replication may occur in human hosts, potentially supported by the slow turnover of the respiratory epithelium. Notably, replication beyond 50-60 days was associated with the accumulation of genetic variations, suggesting a potential mechanism for the emergence of novel variants. To mitigate this risk, limiting transmission to within 50-60 days may be preferable. This issue is particularly relevant in immunocompromised individuals, where prolonged infection may promote viral evolution. Together, these findings provide insight into the replication dynamics of respiratory viruses in human tissue and highlight the importance of limiting long-term replication to prevent the emergence of new variants.