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Abstract
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: RV2 healthy control subjects (n = 37), RV1 asymptomatic subjects (n = 14), RV1 outpatients (n = 30), and RV1 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 RV1 subjects. Unsupervised hierarchical clustering identified two main clusters of subjects. The first included 93% of healthy control subjects and 100% of asymptomatic RV1 subjects, and the second comprised 98% of RV1 inpatients and 88% of RV1 outpatients. Genomic scores of healthy control subjects and asymptomatic RV1 children were similar and significantly lower than those of RV1 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.
Keywords: asymptomatic; children; rhinovirus; transcriptional profiling; viral detection
Rhinoviruses (RVs) are the most frequent etiologic agents of respiratory tract infections, both in children and in adults. In children, the clinical spectrum of RV infection ranges from fever or mild upper respiratory tract infections, such as the common cold and acute otitis media, to severe lower respiratory tract infections, including bronchiolitis, asthma exacerbations, and pneumonia (1-5). In addition, RV-induced wheezing during infancy has been linked to an increased risk for recurrent wheezing and asthma later in childhood (6, 7).
The use of molecular diagnostics has broadened the understanding of RV-associated illnesses. It has also shown that RV can frequently be detected...