Murine parainfluenza virus persists in lung innate immune cells sustaining chronic lung pathology
Ítalo Araújo Castro1,2, Yanling Yang1,2, Victoria Gnazzo1,2
1Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO, USA.
Abstract:
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.
Insights
Human parainfluenza viruses can persist in lung immune cells after infection, driving chronic lung diseases like asthma. Targeting these infected cells can significantly reduce disease severity.
Area of Science:
- Immunology
- Virology
- Respiratory Medicine
Background:
- Respiratory viruses, including human parainfluenza viruses, pose seasonal threats and are linked to chronic lung diseases.
- The persistence of viral products and their role in chronic respiratory disease pathogenesis remain unclear.
Purpose of the Study:
- To investigate the in vivo persistence of viral products after parainfluenza virus infection.
- To determine the impact of persistent viral products on chronic lung disease development, including asthma.
- To identify cellular sources of persistent viral products and their contribution to chronic pathology.
Main Methods:
- Utilized the murine parainfluenza virus Sendai model.
- Employed techniques to detect persistent viral protein and RNA in lung cells.
- Performed transcriptomic analysis to identify inflammation-related signatures.
- Used lineage tracing to map cellular contributions to chronic pathology.
- Conducted targeted ablation of infected cells to assess therapeutic impact.
Main Results:
- Viral protein and RNA were found to persist in lung macrophages, type 2 innate lymphoid cells (ILC2s), and dendritic cells post-infection.
- Cells with persistent viral protein exhibited Th2 inflammation signatures associated with chronic lung diseases like asthma.
- Distinct cell populations were identified as contributors to chronic lung pathology.
- Targeted elimination of infected cells led to significant amelioration of chronic lung disease.
Conclusions:
- Persistent infection of innate immune cells is a critical factor in the transition from acute viral infection to chronic lung disease.
- Innate immune cells harbor persistent viral components that can drive chronic respiratory pathology.
- Understanding and targeting these persistent infections offers a potential therapeutic strategy for chronic lung diseases following viral infections.
