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Updated: Jun 10, 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
Reduced antiviral gene expression and elevated CXCL8 expression in peripheral blood are associated with severe
Carlos Pita-Martínez1, Carmen Goez-Sanz2,3, Ana Virseda-Berdices1,4
1Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain.
Insights
In children with respiratory syncytial virus (RSV) infection, higher CXCL8 (interleukin-8) gene expression and lower antiviral gene expression are linked to severe hypoxemia. This suggests an inflammatory immune response contributes to severe RSV illness.
Area of Science:
- Immunology
- Virology
- Pediatrics
- Respiratory Medicine
Background:
- The precise pathology of respiratory syncytial virus (RSV) infection, particularly concerning severe hypoxemia, is not fully understood.
- An imbalanced immune response during RSV infection can lead to immunopathology, resulting in airway damage and impaired gas exchange.
Purpose of the Study:
- To investigate the association between the expression of specific inflammatory and antiviral genes in peripheral blood and the occurrence of severe hypoxemia in children hospitalized with RSV infection.
- To identify potential biomarkers indicative of severe disease progression in pediatric RSV cases.
Main Methods:
- A cross-sectional study involving 121 children diagnosed with RSV infection.
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure the expression levels of genes including IL-6, TNFα, CXCL8, ISG15, IFIT1, RIGI, IFNβ, CCL5, and CXCL10 in whole blood samples.
- Severe hypoxemia was defined as oxygen saturation (SpO2) ≤ 90%. Statistical analyses included volcano plots, adjusted logistic regression, and orthogonal partial least squares discriminant analysis (OPLS-DA).
Main Results:
- Twenty-six out of 121 children (21.5%) presented with severe hypoxemia.
- Significantly higher expression of CXCL8 (interleukin-8) and significantly lower expression of antiviral genes (ISG15, IFIT1, RIGI, IFNβ, CCL5, CXCL10) were observed in children with severe hypoxemia compared to those without.
- OPLS-DA identified CXCL8, ISG15, IFIT1, RIGI, and CXCL10 as key differentiating genes (Variable Importance in Projection [VIP] ≥1).
Conclusions:
- An immune response skewed towards inflammation over antiviral defense appears to play a critical role in the pathogenesis of severe hypoxemia in pediatric RSV infections.
- These gene expression patterns offer valuable insights into RSV disease mechanisms and may aid in identifying children at risk for severe outcomes.
Abstract:
The pathology of respiratory syncytial virus (RSV) infection remains unclear. An unbalanced immune response to RSV infection can lead to immunopathology, causing airway damage and impaired exchange of oxygen and carbon dioxide between the air and the bloodstream. We aimed to evaluate the association of the expression of inflammatory and antiviral genes in peripheral blood with severe hypoxemia in children with RSV infection seen in the hospital emergency room. We conducted a cross-sectional study on 121 RSV-infected children seen in hospital emergency rooms between 2015 and 2023. Total RNA was extracted from whole blood samples, and gene expression (IL-6, TNFα, CXCL8, ISG15, IFIT1, RIGI, IFNβ, CCL5, and CXCL10) was quantified using quantitative RT-PCR. The outcome variable was having severe hypoxemia (SpO2 ≤ 90%). The association analysis was performed using a volcano plot, adjusted logistic regression, and orthogonal partial least squares discriminant analysis (OPLS-DA). We found that 26 of 121 children had severe hypoxemia (SpO2 ≤ 90%). CXCL8 was overexpressed [fold changes (FC) > 2; q-value < 0.05], and ISG15, IFIT1, RIGI, IFNβ, CCL5, and CXCL10 were underexpressed (FC <0.5; q-value <0.05) in children with severe hypoxemia. These associations were ratified using adjusted logistic regression. The OPLS-DA showed that the gene expressions of CXCL8, ISG15, IFIT1, RIGI, and CXCL10 had values of variable importance in projection (VIP) ≥1, being the most relevant features. In conclusion, an imbalance favoring inflammation over antiviral defense may contribute to the pathogenesis of severe hypoxemia in RSV-infected children. These findings provide valuable insights into the pathology of RSV infection.
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