Development of Respiratory Syncytial Virus “Bronchiolitis” in Guinea Pigs Does Not Reflect an Allergic Predisposition in the Host

doi:10.1378/chest.124.2.671

Chest

Volume 124, Issue 2, August 2003, Pages 671-681

https://doi.org/10.1378/chest.124.2.671 Get rights and content

Background

Respiratory syncytial virus (RSV) infection causes bronchiolitis in a minority of children. Using a guinea pig model to determine if an allergic predisposition in the host increases permissiveness to RSV infection or severity of experimental “bronchiolitis,” we compared the effects of RSV inoculation between strain 2 (allergy-resistant) and strain 13 (allergy-susceptible) inbred animals.

Methods

One month-old, juvenile guinea pigs were classified into four groups (eight guinea pigs per group): (group 1) strain 2, uninfected; (group 2) strain 13, uninfected; (group 3) strain 2, RSV infected; and (group 4) strain 13, RSV infected. Seven days after inoculation, the animals were studied by the following: viral plaque assays for quantification of intrapulmonary RSV; immunohistochemical localization of RSV antigens in lung tissue sections; physiologic assessment of airway obstruction and nonspecific bronchial hyperresponsiveness; quantitative histology of airway T lymphocytes, neutrophils, and eosinophils; and semiquantitative reverse transcriptase-polymerase chain reaction for levels of messenger RNA expression of a panel of proinflammatory cytokines and chemokines.

Results

Significantly higher titers of replicating RSV were isolated from the lungs of strain 13 vs strain 2 animals (p ≤ 0.001). The two guinea pig strains showed similar cell types with positive viral immunostaining; RSV-associated changes in airway obstruction and nonspecific bronchial hyperresponsiveness; airway T cells, neutrophils, and eosinophils; and messenger RNA expression of cytokines and chemokines.

Conclusions

Strain 13 guinea pigs show increased pulmonary RSV replication than strain 2 animals, but this increased permissiveness to the virus is not reflected by more severe virus-induced changes in airway obstruction, nonspecific bronchial hyperresponsiveness, airway inflammation, or gene expression of proinflammatory cytokines and chemokines.

Section snippets

Animals

Sixteen 1-month old, strain 2 guinea pigs (body weight, 250 to 300 g) were purchased from the Cancer Research Centre, Frederick, MD; and 16 strain 13 guinea pigs matched for age, sex, and body weight were obtained from Fort Detrick, MD. Animals were housed in the animal care facility of the McDonald Research Laboratories and iCAPTURE Centre at St. Paul’s Hospital under conditions of alternating 12-h light-dark cycles, plastic cages with hypoallergenic bedding, and free access to food and water,

Results

The viral and sham inoculation procedures were well tolerated by all animals studied. No deaths occurred prior to euthanasia; in virus-inoculated animals, there were no instances of abnormal breathing, decreased activity or feeding, loss of fur, or other signs to suggest severe clinical symptomatology associated with experimental RSV infection.

Discussion

In this study, we experimentally inoculated human RSV into the lungs of allergy-resistant strain 2 and allergy-susceptible strain 13 inbred guinea pigs, to determine the effect of a host’s genetic predisposition for allergy on the development of experimental bronchiolitis. The results showed that 7 days after the inoculation procedure, RSV infection of strain 13 animals was associated with a significant increase in viral pfu per unit weight of lung tissue compared with strain 2 animals (p ≤

ACKNOWLEDGMENT

The authors thank Mr. Stuart Greene and Mr. Dean English for photographic assistance, and Ms. Diane Minshall and Ms. Lynne Carter for assistance in care of experimental animals.

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: Financial support was provided by the Canadian Institutes of Health Research and the British Columbia Lung Association.

: Financial support for Dr. Khan was provided by the Faculty of Health Sciences, Aga Khan University, Karachi, Pakistan.

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Chest

Laboratory and Animal InvestigationsDevelopment of Respiratory Syncytial Virus “Bronchiolitis” in Guinea Pigs Does Not Reflect an Allergic Predisposition in the Host*

Background

Methods

Results

Conclusions

Section snippets

Animals

Results

Discussion

ACKNOWLEDGMENT

Am J Hum Genet

Lancet

Cytokine

Microbes Infect

Chest

Respiratory syncytial virus and parainfluenza virus

N Engl J Med

Respiratory syncytial virus

Decreased interleukin-12 levels in umbilical cord blood in children who developed acute bronchiolitis

Pediatr Pulmonol

Atopy predisposing to acute bronchiolitis during an epidemic of respiratory syncytial virus

BMJ Clin Res Ed

Atopy does not predispose to RSV bronchiolitis or post-bronchiolitic wheezing

BMJ

Eosinophil cationic protein in nasal secretion and in serum and myeloperoxidase in serum in respiratory syncytial virus bronchiolitis: relation to asthma and atopy

Acta Pediatrica

A comparison of cytokine responses in respiratory syncytial virus and influenza A infections in infants

Eur J Pediatr

Predominant type-2 response in infants with respiratory syncytial virus (RSV) infection demonstrated by cytokine flow cytometry

Clin Exp Allergy

Type 1-like immune response is found in children with respiratory syncytial virus infection regardless of clinical severity

J Med Virol

IL-8 and neutrophil elastase levels in the respiratory tract of infants with RSV bronchiolitis

Eur Respir J

Production of acute bronchiolitis in guinea pigs by human respiratory syncytial virus

Eur Respir J

Increased airway reactivity in human RSV bronchiolitis in the guinea pig is not due to increased wall thickness

Pediatr Pulmonol

Primary respiratory syncytial virus infection in mice

J Med Virol

The pathogenesis of respiratory syncytial virus infection in infant ferrets

Am J Pathol

The pathogenesis of respiratory syncytial virus infection in cotton rats

Am J Pathol

Disturbance in respiratory mechanics in infants with bronchiolitis

Thorax

Laboratory and Animal Investigations
Development of Respiratory Syncytial Virus “Bronchiolitis” in Guinea Pigs Does Not Reflect an Allergic Predisposition in the Host^*