Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice

Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality. RSV is able to evade antiviral defenses to persist in the lungs of COPD patients. Though RSV infection has b...

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Main Authors:	Foronjy, Robert F., Dabo, Abdoulaye J., Taggart, Clifford C., Weldon, Sinead, Geraghty, Patrick
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938768/

id	pubmed-3938768
recordtype	oai_dc
spelling	pubmed-39387682014-03-04 Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice Foronjy, Robert F. Dabo, Abdoulaye J. Taggart, Clifford C. Weldon, Sinead Geraghty, Patrick Research Article Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality. RSV is able to evade antiviral defenses to persist in the lungs of COPD patients. Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established. Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice. RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice. This infiltration of cells was most pronounced around the vasculature and bronchial airways. By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure. Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z) expression. In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure. RSV and smoke exposure also reduced protein phosphatase 2A (PP2A) and protein tyrosine phosphates (PTP1B) expression and activity. This is significant as these phosphatases counter smoke-induced inflammation and protease expression. Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice. Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression. Public Library of Science 2014-02-28 /pmc/articles/PMC3938768/ /pubmed/24587397 http://dx.doi.org/10.1371/journal.pone.0090567 Text en © 2014 Foronjy et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Foronjy, Robert F. Dabo, Abdoulaye J. Taggart, Clifford C. Weldon, Sinead Geraghty, Patrick
spellingShingle	Foronjy, Robert F. Dabo, Abdoulaye J. Taggart, Clifford C. Weldon, Sinead Geraghty, Patrick Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice
author_facet	Foronjy, Robert F. Dabo, Abdoulaye J. Taggart, Clifford C. Weldon, Sinead Geraghty, Patrick
author_sort	Foronjy, Robert F.
title	Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice
title_short	Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice
title_full	Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice
title_fullStr	Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice
title_full_unstemmed	Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice
title_sort	respiratory syncytial virus infections enhance cigarette smoke induced copd in mice
description	Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality. RSV is able to evade antiviral defenses to persist in the lungs of COPD patients. Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established. Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice. RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice. This infiltration of cells was most pronounced around the vasculature and bronchial airways. By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure. Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z) expression. In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure. RSV and smoke exposure also reduced protein phosphatase 2A (PP2A) and protein tyrosine phosphates (PTP1B) expression and activity. This is significant as these phosphatases counter smoke-induced inflammation and protease expression. Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice. Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938768/
_version_	1612063240585478144

Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice

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