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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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Autores principales: Limkar, Ajinkya R., Percopo, Caroline M., Redes, Jamie L., Druey, Kirk M., Rosenberg, Helene F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143513/
https://www.ncbi.nlm.nih.gov/pubmed/33922096
http://dx.doi.org/10.3390/v13050728
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author Limkar, Ajinkya R.
Percopo, Caroline M.
Redes, Jamie L.
Druey, Kirk M.
Rosenberg, Helene F.
author_facet Limkar, Ajinkya R.
Percopo, Caroline M.
Redes, Jamie L.
Druey, Kirk M.
Rosenberg, Helene F.
author_sort Limkar, Ajinkya R.
collection PubMed
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.
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spelling pubmed-81435132021-05-25 Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice Limkar, Ajinkya R. Percopo, Caroline M. Redes, Jamie L. Druey, Kirk M. Rosenberg, Helene F. Viruses Article 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. MDPI 2021-04-22 /pmc/articles/PMC8143513/ /pubmed/33922096 http://dx.doi.org/10.3390/v13050728 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Limkar, Ajinkya R.
Percopo, Caroline M.
Redes, Jamie L.
Druey, Kirk M.
Rosenberg, Helene F.
Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143513/
https://www.ncbi.nlm.nih.gov/pubmed/33922096
http://dx.doi.org/10.3390/v13050728
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