Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice
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...
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doaj-e2affcd9dc804446a01372afc6dd90e42021-04-22T23:02:53ZengMDPI AGViruses1999-49152021-04-011372872810.3390/v13050728Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of MiceAjinkya R. Limkar0Caroline M. Percopo1Jamie L. Redes2Kirk M. Druey3Helene F. Rosenberg4Inflammation Immunobiology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAInflammation Immunobiology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USALung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USALung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAInflammation Immunobiology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USARespiratory 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.https://www.mdpi.com/1999-4915/13/5/728respiratory virussublethal infectioninflammationairway hyperresponsiveness |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ajinkya R. Limkar Caroline M. Percopo Jamie L. Redes Kirk M. Druey Helene F. Rosenberg |
spellingShingle |
Ajinkya R. Limkar Caroline M. Percopo Jamie L. Redes Kirk M. Druey Helene F. Rosenberg Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice Viruses respiratory virus sublethal infection inflammation airway hyperresponsiveness |
author_facet |
Ajinkya R. Limkar Caroline M. Percopo Jamie L. Redes Kirk M. Druey Helene F. Rosenberg |
author_sort |
Ajinkya R. Limkar |
title |
Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice |
title_short |
Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice |
title_full |
Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice |
title_fullStr |
Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice |
title_full_unstemmed |
Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice |
title_sort |
persistent airway hyperresponsiveness following recovery from infection with pneumonia virus of mice |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2021-04-01 |
description |
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. |
topic |
respiratory virus sublethal infection inflammation airway hyperresponsiveness |
url |
https://www.mdpi.com/1999-4915/13/5/728 |
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