Differential pathogenesis of respiratory syncytial virus clinical isolates in BALB/c mice

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Airway mucus is a hallmark of respiratory syncytial virus (RSV) lower respiratory tract illness. Laboratory RSV strains differentially induce airway mucus production in mice. Here, we tested the hypothesis that RSV strains differ in pathogenesis by screening six low-passage RSV clinical isolates for mucogenicity and virulence in BALB/cJ mice. The RSV clinical isolates induced variable disease severity, lung interleukin-13 (IL-13) levels, and gob-5 levels in BALB/cJ mice. We chose two of these clinical isolates for further study. Infection of BALB/cJ mice with RSV A2001/2-20 (2-20) resulted in greater disease severity, higher lung IL-13 levels, and higher lung gob-5 levels than infection with RSV strains A2, line 19, Long, and A2001/3-12 (3-12). Like the line 19 RSV strain, the 2-20 clinical isolate induced airway mucin expression in BALB/cJ mice. The 2-20 and 3-12 RSV clinical isolates had higher lung viral loads than laboratory RSV strains at 1 day postinfection (p.i.). This increased viral load correlated with higher viral antigen levels in the bronchiolar epithelium and greater histopathologic changes at 1 day p.i. The A2 RSV strain had the highest peak viral load at day 4 p.i. RSV 2-20 infection caused epithelial desquamation, bronchiolitis, airway hyperresponsiveness, and increased breathing effort in BALB/cJ mice. We found that RSV clinical isolates induce variable pathogenesis in mice, and we established a mouse model of clinical isolate strain-dependent RSV pathogenesis that recapitulates key features of RSV disease.

Author-supplied keywords

  • *Disease Models, Animal
  • Animals
  • Cell Line
  • Chloride Channels/metabolism
  • Female
  • Humans
  • Interleukin-13/metabolism
  • Lung/metabolism/pathology/virology
  • Mice
  • Molecular Sequence Data
  • Mucins/metabolism
  • Mucoproteins/metabolism
  • Respiratory Syncytial Virus Infections/pathology/*
  • Respiratory Syncytial Virus, Human/classification/
  • Sequence Analysis, DNA
  • Severity of Illness Index
  • Species Specificity
  • Viral Fusion Proteins
  • Viral Load
  • Virulence
  • purification/*pathogenicity

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  • World Health Organization

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