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Updated: Mar 30, 2026

High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions
Published on: March 5, 2022
Rhinovirus Detection in Symptomatic and Asymptomatic Children: Value of Host Transcriptome Analysis
Santtu Heinonen1, Tuomas Jartti2, Carla Garcia3
11 Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, and.
Insights
Host transcriptional profiling can distinguish symptomatic rhinovirus (RV) infections from asymptomatic RV detection in children. This method effectively identifies active RV infections by analyzing immune gene expression patterns.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Rhinoviruses (RVs) are common causes of respiratory infections across all age groups.
- RVs are frequently detected in individuals without symptoms.
Purpose of the Study:
- To assess if host transcriptional profiling can differentiate symptomatic RV infections from incidental RV detection in children.
- To analyze immune gene expression differences between symptomatic and asymptomatic RV cases.
Main Methods:
- Whole-blood RNA transcriptional profiles were analyzed in 151 children under 2 years old.
- Children were categorized into four groups: RV- healthy controls, RV+ asymptomatic, RV+ outpatients, and RV+ inpatients.
- Quantitative real-time polymerase chain reaction (qRT-PCR) was used for validation.
Main Results:
- Symptomatic RV infection triggered a distinct transcriptional signature, validated across cohorts.
- Symptomatic infections showed overexpression of innate immunity genes and underexpression of adaptive immunity genes.
- Asymptomatic RV detection was associated with minimal transcriptional changes, clustering similarly to healthy controls.
Conclusions:
- Symptomatic RV infection generates a reproducible host transcriptional signature.
- Incidental RV detection in asymptomatic children does not induce significant systemic immune responses.
- Transcriptional profiling is a valuable tool for distinguishing active RV infection from asymptomatic carriage.
Rationale:
Rhinoviruses (RVs) are a major cause of symptomatic respiratory tract infection in all age groups. However, RVs can frequently be detected in asymptomatic individuals.
Objectives:
To evaluate the ability of host transcriptional profiling to differentiate between symptomatic RV infection and incidental detection in children.
Methods:
Previously healthy children younger than 2 years old (n = 151) were enrolled at four study sites and classified into four clinical groups: RV- healthy control subjects (n = 37), RV+ asymptomatic subjects (n = 14), RV+ outpatients (n = 30), and RV+ inpatients (n = 70). Host responses were analyzed using whole-blood RNA transcriptional profiles.
Measurements And Main Results:
RV infection induced a robust transcriptional signature, which was validated in three independent cohorts and by quantitative real-time polymerase chain reaction with high prediction accuracy. The immune profile of symptomatic RV infection was characterized by overexpression of innate immunity and underexpression of adaptive immunity genes, whereas negligible changes were observed in asymptomatic RV+ subjects. Unsupervised hierarchical clustering identified two main clusters of subjects. The first included 93% of healthy control subjects and 100% of asymptomatic RV+ subjects, and the second comprised 98% of RV+ inpatients and 88% of RV+ outpatients. Genomic scores of healthy control subjects and asymptomatic RV+ children were similar and significantly lower than those of RV+ inpatients and outpatients (P < 0.0001).
Conclusions:
Symptomatic RV infection induced a robust and reproducible transcriptional signature, whereas identification of RV in asymptomatic children was not associated with significant systemic transcriptional immune responses. Transcriptional profiling represents a useful tool to discriminate between active infection and incidental virus detection.
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