Murine Parainfluenza Virus Persists in Lung Innate Immune Cells Sustaining Chronic Lung Pathology

Respiratory viruses including the human parainfluenza viruses (hPIVs) are a constant burden to human health, with morbidity and mortality frequently increased after the acute phase of the infection. Although is proven that respiratory viruses can persist in vitro, the mechanisms of virus or viral products persistence, their sources, and their impact on chronic respiratory diseases in vivo are unknown. Here, we used Sendai virus (SeV) to model hPIV infection in mice and test whether virus persistence associates with the development of chronic lung disease. Following SeV infection, virus products were detected in lung macrophages, type 2 innate lymphoid cells (ILC2s) and dendritic cells for several weeks after the infectious virus was cleared. Cells containing viral protein showed strong upregulation of antiviral and type 2 inflammation-related genes that associate with the development of chronic post-viral lung diseases, including asthma. Lineage tracing of infected cells or cells derived from infected cells suggests that distinct functional groups of cells contribute to the chronic pathology. Importantly, targeted ablation of infected cells or those derived from infected cells significantly ameliorated chronic lung disease. Overall, we identified persistent infection of innate immune cells as a critical factor in the progression from acute to chronic post viral respiratory disease.