Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO, USA.
Center for Women's Infectious Diseases Research, Washington University School of Medicine, Saint Louis, MO, USA.
Nat Microbiol. 2024 Nov;9(11):2803-2816. doi: 10.1038/s41564-024-01805-8. Epub 2024 Oct 2.
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，并与慢性肺部疾病的发展有关。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不清楚。利用鼠副流感病毒仙台株，我们证明了病毒蛋白和 RNA 在传染性病毒清除后很长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。含有持续病毒蛋白的细胞表达与慢性肺部疾病（包括哮喘）发展相关的 Th2 炎症相关转录组特征。谱系追踪表明，不同功能群的细胞有助于慢性病理学的发展。重要的是，靶向清除感染细胞可显著改善慢性肺部疾病。总的来说，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部疾病向慢性肺部疾病发展的关键因素。
