Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice.
Ajinkya R LimkarCaroline M PercopoJamie L RedesKirk M DrueyHelene F RosenbergPublished in: Viruses (2021)
Respiratory virus infections can have long-term effects on lung function that persist even after the acute responses have resolved. Numerous studies have linked severe early childhood infection with respiratory syncytial virus (RSV) to the development of wheezing and asthma, although the underlying mechanisms connecting these observations remain unclear. Here, we examine airway hyperresponsiveness (AHR) that develops in wild-type mice after recovery from symptomatic but sublethal infection with the natural rodent pathogen, pneumonia virus of mice (PVM). We found that BALB/c mice respond to a limited inoculum of PVM with significant but reversible weight loss accompanied by virus replication, acute inflammation, and neutrophil recruitment to the airways. At day 21 post-inoculation, virus was no longer detected in the airways and the acute inflammatory response had largely resolved. However, and in contrast to most earlier studies using the PVM infection model, all mice survived the initial infection and all went on to develop serum anti-PVM IgG antibodies. Furthermore, using both invasive plethysmography and precision-cut lung slices, we found that these mice exhibited significant airway hyperresponsiveness at day 21 post-inoculation that persisted through day 45. Taken together, our findings extend an important and versatile respiratory virus infection model that can now be used to explore the role of virions and virion clearance as well as virus-induced inflammatory mediators and their signaling pathways in the development and persistence of post-viral AHR and lung dysfunction.
Keyphrases
- wild type
- lung function
- high fat diet induced
- cystic fibrosis
- liver failure
- weight loss
- inflammatory response
- respiratory failure
- respiratory syncytial virus
- chronic obstructive pulmonary disease
- oxidative stress
- drug induced
- magnetic resonance
- air pollution
- intensive care unit
- sars cov
- type diabetes
- body mass index
- cell proliferation
- bariatric surgery
- endoplasmic reticulum stress
- extracorporeal membrane oxygenation
- epithelial mesenchymal transition
- roux en y gastric bypass
- skeletal muscle
- metabolic syndrome
- lps induced
- mechanical ventilation