Respiratory syncytial virus persistence in the lungs correlates with airway hyperreactivity in the mouse model

Dora Estripeaut, Juan Pablo Torres, Cynthia S. Somers, Claudia Tagliabue, Shama Khokhar, Vijay G. Bhoj, Steve M. Grube, Aneta Wozniakowski, Ana M. Gomez, Octavio Ramilo, Hasan S. Jafri, Asuncion Mejias

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background. Previous studies in mice showed that respiratory syncytial virus (RSV) infection was associated with RSVRNApersistence. This study was designed to characterize the significance of RSVRNApersistence and its relation to RSV-induced chronic airway disease. Methods. Mice were inoculated with live RSV, UV light-treated RSV, heat-inactivated RSV, or medium. Bronchoalveolar lavage fluid samples were obtained and lung specimens were harvested on days 1, 5, and 42 after inoculation to assess lung inflammation, lung mRNA expression of interleukin (IL)-4, IL-5, IL-15, and interferon (IFN)-γ; RSV loads were assessed by culture and real-time polymerase chain reaction (PCR) and correlated with pulmonary function. Results. During the acute phase of infection, RSV loads as indicated by culture and PCR were significantly higher in mice inoculated with live RSV. On day 42, RSV RNA remained detectable only in mice inoculated with live or UV light-treated RSV. Lung inflammation, IFN-γ:IL-4 mRNA expression ratios, airway obstruction (AO), and airway hyperreactivity (AHR) were significantly increased in mice inoculated with live RSV. AO on day 5 and AHR on day 42 were significantly correlated with RSV RNA copy number in lung samples. Conclusions. Infection with live RSV induced acute and chronic airway disease that was associated with a predominantly Th-1 immune response and RSV RNA persistence that significantly correlated with pulmonary function abnormalities.

Original languageEnglish
Pages (from-to)1435-1443
Number of pages9
JournalJournal of Infectious Diseases
Volume198
Issue number10
DOIs
Publication statusPublished - Nov 15 2008

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Respiratory Syncytial Viruses
Lung
Respiratory Syncytial Virus Infections
Airway Obstruction
RNA
Ultraviolet Rays
Interleukin-4
Interferons
Pneumonia
Chronic Disease
Interleukin-15
Messenger RNA
Interleukin-5
Bronchoalveolar Lavage Fluid
Real-Time Polymerase Chain Reaction
Hot Temperature

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Respiratory syncytial virus persistence in the lungs correlates with airway hyperreactivity in the mouse model. / Estripeaut, Dora; Torres, Juan Pablo; Somers, Cynthia S.; Tagliabue, Claudia; Khokhar, Shama; Bhoj, Vijay G.; Grube, Steve M.; Wozniakowski, Aneta; Gomez, Ana M.; Ramilo, Octavio; Jafri, Hasan S.; Mejias, Asuncion.

In: Journal of Infectious Diseases, Vol. 198, No. 10, 15.11.2008, p. 1435-1443.

Research output: Contribution to journalArticle

Estripeaut, D, Torres, JP, Somers, CS, Tagliabue, C, Khokhar, S, Bhoj, VG, Grube, SM, Wozniakowski, A, Gomez, AM, Ramilo, O, Jafri, HS & Mejias, A 2008, 'Respiratory syncytial virus persistence in the lungs correlates with airway hyperreactivity in the mouse model', Journal of Infectious Diseases, vol. 198, no. 10, pp. 1435-1443. https://doi.org/10.1086/592714
Estripeaut, Dora ; Torres, Juan Pablo ; Somers, Cynthia S. ; Tagliabue, Claudia ; Khokhar, Shama ; Bhoj, Vijay G. ; Grube, Steve M. ; Wozniakowski, Aneta ; Gomez, Ana M. ; Ramilo, Octavio ; Jafri, Hasan S. ; Mejias, Asuncion. / Respiratory syncytial virus persistence in the lungs correlates with airway hyperreactivity in the mouse model. In: Journal of Infectious Diseases. 2008 ; Vol. 198, No. 10. pp. 1435-1443.
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abstract = "Background. Previous studies in mice showed that respiratory syncytial virus (RSV) infection was associated with RSVRNApersistence. This study was designed to characterize the significance of RSVRNApersistence and its relation to RSV-induced chronic airway disease. Methods. Mice were inoculated with live RSV, UV light-treated RSV, heat-inactivated RSV, or medium. Bronchoalveolar lavage fluid samples were obtained and lung specimens were harvested on days 1, 5, and 42 after inoculation to assess lung inflammation, lung mRNA expression of interleukin (IL)-4, IL-5, IL-15, and interferon (IFN)-γ; RSV loads were assessed by culture and real-time polymerase chain reaction (PCR) and correlated with pulmonary function. Results. During the acute phase of infection, RSV loads as indicated by culture and PCR were significantly higher in mice inoculated with live RSV. On day 42, RSV RNA remained detectable only in mice inoculated with live or UV light-treated RSV. Lung inflammation, IFN-γ:IL-4 mRNA expression ratios, airway obstruction (AO), and airway hyperreactivity (AHR) were significantly increased in mice inoculated with live RSV. AO on day 5 and AHR on day 42 were significantly correlated with RSV RNA copy number in lung samples. Conclusions. Infection with live RSV induced acute and chronic airway disease that was associated with a predominantly Th-1 immune response and RSV RNA persistence that significantly correlated with pulmonary function abnormalities.",
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AU - Khokhar, Shama

AU - Bhoj, Vijay G.

AU - Grube, Steve M.

AU - Wozniakowski, Aneta

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N2 - Background. Previous studies in mice showed that respiratory syncytial virus (RSV) infection was associated with RSVRNApersistence. This study was designed to characterize the significance of RSVRNApersistence and its relation to RSV-induced chronic airway disease. Methods. Mice were inoculated with live RSV, UV light-treated RSV, heat-inactivated RSV, or medium. Bronchoalveolar lavage fluid samples were obtained and lung specimens were harvested on days 1, 5, and 42 after inoculation to assess lung inflammation, lung mRNA expression of interleukin (IL)-4, IL-5, IL-15, and interferon (IFN)-γ; RSV loads were assessed by culture and real-time polymerase chain reaction (PCR) and correlated with pulmonary function. Results. During the acute phase of infection, RSV loads as indicated by culture and PCR were significantly higher in mice inoculated with live RSV. On day 42, RSV RNA remained detectable only in mice inoculated with live or UV light-treated RSV. Lung inflammation, IFN-γ:IL-4 mRNA expression ratios, airway obstruction (AO), and airway hyperreactivity (AHR) were significantly increased in mice inoculated with live RSV. AO on day 5 and AHR on day 42 were significantly correlated with RSV RNA copy number in lung samples. Conclusions. Infection with live RSV induced acute and chronic airway disease that was associated with a predominantly Th-1 immune response and RSV RNA persistence that significantly correlated with pulmonary function abnormalities.

AB - Background. Previous studies in mice showed that respiratory syncytial virus (RSV) infection was associated with RSVRNApersistence. This study was designed to characterize the significance of RSVRNApersistence and its relation to RSV-induced chronic airway disease. Methods. Mice were inoculated with live RSV, UV light-treated RSV, heat-inactivated RSV, or medium. Bronchoalveolar lavage fluid samples were obtained and lung specimens were harvested on days 1, 5, and 42 after inoculation to assess lung inflammation, lung mRNA expression of interleukin (IL)-4, IL-5, IL-15, and interferon (IFN)-γ; RSV loads were assessed by culture and real-time polymerase chain reaction (PCR) and correlated with pulmonary function. Results. During the acute phase of infection, RSV loads as indicated by culture and PCR were significantly higher in mice inoculated with live RSV. On day 42, RSV RNA remained detectable only in mice inoculated with live or UV light-treated RSV. Lung inflammation, IFN-γ:IL-4 mRNA expression ratios, airway obstruction (AO), and airway hyperreactivity (AHR) were significantly increased in mice inoculated with live RSV. AO on day 5 and AHR on day 42 were significantly correlated with RSV RNA copy number in lung samples. Conclusions. Infection with live RSV induced acute and chronic airway disease that was associated with a predominantly Th-1 immune response and RSV RNA persistence that significantly correlated with pulmonary function abnormalities.

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