Respiratory syncytial virus induces pneumonia, cytokine response, airway obstruction, and chronic inflammatory infiltrates associated with long-term airway hyperresponsiveness in mice

Hasan S. Jafri, Susana Chávez-Bueno, Asunción Mejías, Ana M. Gómez, Ana M. Ríos, Shahryar S. Nassi, Munira Yusuf, Payal Kapur, Robert D. Hardy, Jeanine Hatfield, Beverly B. Rogers, Karen Krisher, Octavio Ramilo

Research output: Contribution to journalArticle

131 Scopus citations

Abstract

Background. Respiratory syncytial virus (RSV) infection is associated with acute morbidity (e.g., pneumonia and airway obstruction [AO]) and long-term complications (e.g., airway hyperresponsiveness [AHR]). We present a comprehensive evaluation of the acute and chronic phases of RSV respiratory tract infection, using a mouse model. Methods. BALB/c mice were inoculated with RSV and monitored for 154 days. RSV loads and cytokines were measured in bronchoalveolar lavage (BAL) samples. Pneumonia severity was assessed using a standard histopathologic score, and pulmonary function was determined by plethysmography. Results. RSV-infected mice exhibited viral replication that peaked on day 4-5 and became undetectable by day 7. These mice developed acute pneumonia (peak days, 4-5) and chronic pulmonary inflammatory infiltrates that lasted up to 154 days after inoculation. BAL concentrations of tumor necrosis factor-α, interleukin (IL)-6, interferon-γ, IL-4, IL-10, KC (an IL-8 homologue), MIG (CXCL9), RANTES, macrophage inflammatory protein-1α, and eotaxin were significantly higher in RSV-infected mice than in control mice. RSV-infected mice developed acute AO during the first week of infection that persisted for 42 days. RSV-infected mice also showed significant AHR in response to methacholine up to 154 days. Conclusion. This model provides a means to investigate the immunopathogenesis of RSV infection and its association with reactive airway disease.

Original languageEnglish (US)
Pages (from-to)1856-1865
Number of pages10
JournalJournal of Infectious Diseases
Volume189
Issue number10
DOIs
StatePublished - May 15 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Jafri, H. S., Chávez-Bueno, S., Mejías, A., Gómez, A. M., Ríos, A. M., Nassi, S. S., Yusuf, M., Kapur, P., Hardy, R. D., Hatfield, J., Rogers, B. B., Krisher, K., & Ramilo, O. (2004). Respiratory syncytial virus induces pneumonia, cytokine response, airway obstruction, and chronic inflammatory infiltrates associated with long-term airway hyperresponsiveness in mice. Journal of Infectious Diseases, 189(10), 1856-1865. https://doi.org/10.1086/386372