Common respiratory viruses, including the human parainfluenza viruses, threaten human health seasonally and associate with the development of chronic lung diseases. Evidence suggests that these viruses can persist, but the sources of viral products in vivo and their impact on chronic respiratory diseases remain unknown. Using the murine parainfluenza virus Sendai, we demonstrate that viral protein and RNA persist in lung macrophages, type 2 innate lymphoid cells (ILC2s) and dendritic cells long after the infectious virus is cleared. Cells containing persistent viral protein expressed Th2 inflammation-related transcriptomic signatures associated with the development of chronic lung diseases, including asthma. Lineage tracing demonstrated that distinct functional groups of cells contribute to the chronic pathology. Importantly, targeted ablation of infected cells significantly ameliorated chronic lung disease. Overall, we identified persistent infection of innate immune cells as a key factor in the progression from acute to chronic lung disease after infection with parainfluenza virus.

常见的呼吸道病毒，包括人类副流感病毒，季节性地威胁着人类健康，并与慢性肺病的发展有关。有证据表明，这些病毒可以持续存在，但体内病毒产物的来源及其对慢性呼吸道疾病的影响仍然未知。使用鼠副流感病毒仙台病毒，我们证明病毒蛋白和 RNA 在感染性病毒清除后很长一段时间内仍存在于肺巨噬细胞、2 型先天淋巴细胞 （ILC2） 和树突状细胞中。含有持续性病毒蛋白的细胞表达与慢性肺部疾病（包括哮喘）的发展相关的 Th2 炎症相关转录组特征。谱系追踪表明，细胞的不同功能群有助于慢性病理。重要的是，感染细胞的靶向消融可显著改善慢性肺病。总体而言，我们发现先天免疫细胞的持续感染是副流感病毒感染后从急性肺病进展为慢性肺病的关键因素。