Respiratory syncytial virus persistence in the lungs correlates with airway hyperreactivity in the mouse model.
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)-gamma; 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-gamma: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.
Estripeaut
Dora
D
Department of Pediatrics, University of Texas Southwestern Medical Center and Children's Medical Center Dallas, Texas 75390-9063, USA.
Torres
Juan Pablo
JP
Somers
Cynthia S
CS
Tagliabue
Claudia
C
Khokhar
Shama
S
Bhoj
Vijay G
VG
Grube
Steve M
SM
Wozniakowski
Aneta
A
Gomez
Ana M
AM
Ramilo
Octavio
O
Jafri
Hasan S
HS
Mejias
Asuncion
A
D000402:Airway Obstruction / Q000209:etiology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D002460:Cell Line; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000473:pathology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays; D019562:Viral Load; D010948:Viral Plaque Assay
D016207:Cytokines