Asthma affects approximately 27 million individuals in the United States, and various factors contribute to its development. These include exposure to poor air quality, second-hand smoke, and early hospitalization due to viral pneumonia or bronchitis. While some researchers suspected that a connection between serious lung infections and asthma could stem from lingering viruses in the lungs, a clear link between persistent viruses and chronic lung disease had not been proven until recently.
A recent study published in Nature Microbiology utilized Sendai virus (SeV) as a model to investigate the potential correlation between viral persistence and the onset of chronic lung diseases in murine systems. Following SeV infection, viral products were detected in lung macrophages, type 2 innate lymphoid cells (ILC2s), and dendritic cells for several weeks post-clearance of the infectious virus. The infected cells demonstrated a significant upregulation of genes associated with antiviral responses and type 2 inflammation, both of which are implicated in the development of chronic post-viral lung conditions, including asthma.
Lineage tracing analyses indicated that distinct functional subsets of cells contribute to chronic pathology. Notably, the targeted ablation of infected cells or their progeny led to a significant reduction in the severity of chronic lung disease. These results highlight that the persistence of viral products within innate immune cells modifies their behaviour, promoting a more inflammatory phenotype compared to uninfected immune cells. This sustained inflammatory response can precipitate chronic lung diseases, as evidenced by persistent signs of inflammation in the lungs of infected mice, including inflamed alveoli, vascular abnormalities, aberrant lung cell development, and excessive immune tissue accumulation.
Castro et al. emphasized the significance of these findings, demonstrating that a common respiratory virus can endure in immunocompetent hosts well beyond the acute phase of infection, leading to chronic pulmonary conditions. This viral persistence elucidates the long-term health consequences often observed in individuals who are believed to have fully recovered from acute respiratory infections.
The implications of this research extend to understanding the etiology of chronic lung diseases and informing potential preventive strategies. Given that the majority of children are exposed to respiratory viruses, such as parainfluenza or respiratory syncytial virus (RSV), by the age of three—with a subset experiencing severe illness—grasping the mechanisms underlying viral persistence in the lungs is vital for mitigating long-term damage.
In conclusion, while it may be challenging to prevent initial infections with these prevalent respiratory viruses, elucidating the persistence and impact of these infections on lung health could inform future strategies aimed at reducing the risk of chronic lung diseases, such as asthma.
References
- Castro ÍA, Yang Y, Gnazzo V, Kim DH, Van Dyken SJ, López CB. Murine parainfluenza virus persists in lung innate immune cells sustaining chronic lung pathology. Nat Microbiol. 2024 Oct 2;1–14.
- Castro ÍA, Yang Y, Gnazzo V, Kim DH, Van Dyken SJ, López CB. Murine Parainfluenza Virus Persists in Lung Innate Immune Cells Sustaining Chronic Lung Pathology. bioRxiv. 2023 Nov 8;2023.11.07.566103.
- Shi T, McAllister DA, O’Brien KL, Simoes EAF, Madhi SA, Gessner BD, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. 2017 Sep 2;390(10098):946–58.