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Updated: Dec 14, 2025
An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
In vivo comparison of a laboratory-adapted and clinical-isolate-based recombinant human respiratory syncytial virus
Laurine C Rijsbergen1, Linda J Rennick2,3, Brigitta M Laksono1
1Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus MC, Rotterdam, The Netherlands.
Insights
This study reveals that a clinical Human Respiratory Syncytial Virus (HRSV) strain replicates better in animal models than a lab-adapted strain. Understanding HRSV pathogenesis requires using representative clinical virus strains for accurate in vivo research.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Human respiratory syncytial virus (HRSV) is a major cause of infant respiratory illness.
- Limited understanding of HRSV pathogenesis and disease severity factors exists, partly due to lab-adapted virus strains.
- Early viral dissemination and tropism are key to understanding HRSV infection.
Purpose of the Study:
- To investigate early viral dissemination and tropism of HRSV in animal models.
- To compare a novel clinical HRSV strain (A11) with a laboratory-adapted strain.
- To determine the impact of virus strain choice on HRSV pathogenesis studies.
Main Methods:
- Utilized recombinant HRSV strains expressing EGFP in cotton rats and mice (BALB/cJ, C57BL/6).
- Compared viral replication and dissemination of a clinical isolate (rHRSVA11EGFP(5)) versus a lab-adapted strain (rHRSVA2EGFP(5)).
- Analyzed infected cell tropism in the upper and lower respiratory tracts.
Main Results:
- The clinical rHRSVA11EGFP(5) strain showed higher viral titers in the upper respiratory tract of cotton rats and mice compared to the lab-adapted strain.
- HRSV infection was detected in nasal septa and lungs by day 2 post-inoculation.
- Tropism differed, with infection in ciliated epithelial cells of cotton rats and olfactory mucosa of mice.
Conclusions:
- The choice of HRSV strain is critical for accurate in vivo pathogenesis studies.
- The A11 strain serves as a representative clinical virus for research.
- Significant differences in tropism and inflammation were observed between cotton rats and mice during HRSV infection.
Abstract:
Human respiratory syncytial virus (HRSV) is the leading cause of severe respiratory tract disease in infants. Most HRSV infections remain restricted to the upper respiratory tract (URT), but in a small percentage of patients the infection spreads to the lower respiratory tract, resulting in bronchiolitis or pneumonia. We have a limited understanding of HRSV pathogenesis and what factors determine disease severity, partly due to the widespread use of tissue-culture-adapted viruses. Here, we studied early viral dissemination and tropism of HRSV in cotton rats, BALB/cJ mice and C57BL/6 mice. We used a novel recombinant (r) strain based on a subgroup A clinical isolate (A11) expressing EGFP [rHRSVA11EGFP(5)]. A recombinant laboratory-adapted HRSV strain [rHRSVA2EGFP(5)] was used as a direct comparison. Our results show that rHRSVA11EGFP(5) replicated to higher viral titres than laboratory-adapted rHRSVA2EGFP(5) in the URT of cotton rats and mice. HRSV-infected cells were detected as early as 2 days post-inoculation in both species in the nasal septa and lungs. Infection was predominantly present in ciliated epithelial cells in cotton rats and in the olfactory mucosa of mice. In our opinion, this study highlights that the choice of virus strain is important when studying HRSV pathogenesis in vivo and demonstrates that A11 is a representative clinical-based virus. Additionally, we show critical differences in tropism and inflammation when comparing HRSV infection of cotton rats and mice.
