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Updated: Mar 31, 2026
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
Viral Specific Factors Contribute to Clinical Respiratory Syncytial Virus Disease Severity Differences in Infants
Tonya M Thompson1, Philippa L Roddam2, Lisa M Harrison2
1University of Tennessee School of Medicine, Department of Pediatrics ; University of Arkansas for Medical Sciences, Department of Pediatric Emergency Medicine, Little Rock, AR 72202.
Insights
Viral factors, not just host factors, may influence respiratory syncytial virus (RSV) disease severity in infants. Certain RSV strains induce higher cytokine and chemokine levels, potentially explaining differences in illness severity.
Area of Science:
- Virology
- Immunology
- Pediatrics
Background:
- Respiratory Syncytial Virus (RSV) causes variable disease severity in infants.
- Host factors are known contributors to RSV disease severity.
- Viral intrinsic factors' role in RSV severity is understudied.
Purpose of the Study:
- To investigate if RSV isolates from infants with differing disease severities induce distinct cytokine/chemokine responses.
- To assess phenotypic differences in viral isolates independent of host factors.
Main Methods:
- Low-passage RSV isolates from hospitalized (severe) and non-hospitalized (mild) infants were used.
- Human lung epithelial cells (A549) were infected with RSV isolates at a controlled multiplicity of infection.
- Cytokine/chemokine concentrations (IL-1α, IL-6, IL-8, RANTES) and viral load were measured at 48, 60, and 72 hours.
Main Results:
- Isolates from severely ill infants induced significantly higher concentrations of all tested cytokines/chemokines compared to mild disease isolates.
- RSV isolates from severe cases induced higher IL-8 and RANTES secretion (p=0.028, p=0.019).
- Higher viral load correlated significantly with increased IL-8 and RANTES levels.
Conclusions:
- Intrinsic viral characteristics may contribute to the varying severity of RSV disease in infants.
- Specific RSV strains may elicit stronger inflammatory responses, influencing disease outcomes.
Background:
There is a wide range of severity of respiratory syncytial viral (RSV) disease in previously healthy infants. Host factors have been well demonstrated to contribute to disease severity differences. However the possibility of disease severity differences being produced by factors intrinsic to the virus itself has rarely been studied.
Methods:
Low-passage isolates of RSV collected prospectively from infants with different degrees of RSV disease severity were evaluated in vitro, holding host factors constant, so as to assess whether isolates induced phenotypically different cytokine/chemokine concentrations in a human lung epithelial cell line. Sixty-seven RSV isolates from previously healthy infants (38 hospitalized for acute RSV infection (severe disease) and 29 never requiring hospitalization (mild disease)) were inoculated into A549, lung epithelial cells at precisely controlled, low multiplicity of infection to mimic natural infection. Cultures were evaluated at 48 hours, 60 hours, and 72 hours to evaluate area under the curve (AUC) cytokine/chemokine induction.
Results:
Cells infected with isolates from severely ill infants produced higher mean concentrations of all cytokine/chemokines tested (IL-1α, IL-6, IL-8 and RANTES) at all-time points tested. RSV isolates collected from infants with severe disease induced significantly higher AUCIL-8 and AUCRANTES secretion in infected cultures than mild disease isolates (p=0.028 and p=0.019 respectively). IL-8 and RANTES concentrations were 4 times higher at 48 hours for these severely ill infant isolates. Additionally, 38 isolates were evaluated at all-time points for quantity of virus. RSV concentration significantly correlated with both IL-8 and RANTES at all-time points. Neither cytokine/chemokine concentrations nor RSV concentrations were associated with RSV subgroup.
Discussion:
Infants' RSV disease severity differences may be due in part to intrinsic viral strain-specific characteristics.
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