Respiratory Syncytial Virus Persistence in the Lungs Correlates with Airway Hyperreactivity in the Mouse Model

• Published in: The Journal of infectious diseases Vol. 198; no. 10; pp. 1435 - 1443
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15-11-2008; University of Chicago Press
• Subjects: Airway Obstruction - etiology; Animals; Biological and medical sciences; Bronchial Hyperreactivity - etiology; Bronchoalveolar Lavage Fluid - virology; Cell Line; Cytokines - genetics; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Human respiratory syncytial virus; Humans; Infections; Infectious diseases; Inoculation; Lung - pathology; Lung - virology; Lungs; Medical sciences; Messenger RNA; Mice; Mice, Inbred BALB C; Microbiology; Pneumonia; Polymerase chain reaction; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - complications; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - pathology; Respiratory Syncytial Virus Infections - virology; Respiratory syncytial viruses; Respiratory Syncytial Viruses - immunology; Respiratory Syncytial Viruses - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA; Ultraviolet Rays; Viral Load; Viral Plaque Assay; Viruses; Infection; Respiratory tract; Animal model; Microbiology; Respiratory system; Lung
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/592714

Background. Previous studies in mice showed that respiratory syncytial virus (RSV) infection was associated with RSV RNA persistence. This study was designed to characterize the significance of RSV RNA persistence 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.