Respiratory syncytial virus-induced acute and chronic airway disease is independent of genetic background: an experimental murine model.
BACKGROUND
Respiratory syncytial virus (RSV) is the leading respiratory viral pathogen in young children worldwide. RSV disease is associated with acute airway obstruction (AO), long-term airway hyperresponsiveness (AHR), and chronic lung inflammation. Using two different mouse strains, this study was designed to determine whether RSV disease patterns are host-dependent. C57BL/6 and BALB/c mice were inoculated with RSV and followed for 77 days. RSV loads were measured by plaque assay and polymerase chain reaction (PCR) in bronchoalveolar lavage (BAL) and whole lung samples; cytokines were measured in BAL samples. Lung inflammation was evaluated with a histopathologic score (HPS), and AO and AHR were determined by plethysmography.


RESULTS
Viral load dynamics, histopathologic score (HPS), cytokine concentrations, AO and long-term AHR were similar in both strains of RSV-infected mice, although RSV-infected C57BL/6 mice developed significantly greater AO compared with RSV-infected BALB/c mice on day 5. PCR detected RSV RNA in BAL samples of RSV infected mice until day 42, and in whole lung samples through day 77. BAL concentrations of cytokines TNF-alpha, IFN-gamma, and chemokines MIG, RANTES and MIP-1alpha were significantly elevated in both strains of RSV-infected mice compared with their respective controls. Viral load measured by PCR significantly correlated with disease severity on days 14 and 21.


CONCLUSIONS
RSV-induced acute and chronic airway disease is independent of genetic background.
Chávez-Bueno
Susana
S
Division of Pediatric Infectious Diseases, Department of Pediatrics, The University of Texas Southwestern Medical Center, Children's Medical Center, Dallas, Texas, USA. susana.chavez-bueno@utsouthwestern.edu
Mejías
Asunción
A
Gómez
Ana M
AM
Olsen
Kurt D
KD
Ríos
Ana M
AM
Fonseca-Aten
Mónica
M
Ramilo
Octavio
O
Jafri
Hasan S
HS
D000402:Airway Obstruction / Q000235:genetics / Q000473:pathology / Q000821:virology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions / Q000235:genetics*; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012367:RNA, Viral / Q000032:analysis; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000302:isolation & purification / Q000502:physiology; D019562:Viral Load
D016207:Cytokines; D012367:RNA, Viral