• Santtu Heinonen, Tuomas Jartti, Carla Garcia, Silvia Oliva, Cynthia Smitherman, Esperanza Anguiano, Wouter A A de Steenhuijsen Piters, Tytti Vuorinen, Olli Ruuskanen, Blerta Dimo, Nicolas M Suarez, Virginia Pascual, Octavio Ramilo, and Asuncion Mejias.
• 1 Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, and.
• Am. J. Respir. Crit. Care Med. 2016 Apr 1; 193 (7): 772-82.

RationaleRhinoviruses (RVs) are a major cause of symptomatic respiratory tract infection in all age groups. However, RVs can frequently be detected in asymptomatic individuals.ObjectivesTo evaluate the ability of host transcriptional profiling to differentiate between symptomatic RV infection and incidental detection in children.MethodsPreviously 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 ResultsRV 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).ConclusionsSymptomatic 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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