Rhinovirus detection in symptomatic and asymptomatic children value of host transcriptome analysis

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, Asuncion Mejias

Research output: Contribution to journalArticle

37 Citations (Scopus)

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%ofasymptomatic RV1subjects, andthesecond comprised98% 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.

Original languageEnglish (US)
Pages (from-to)772-782
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume193
Issue number7
DOIs
StatePublished - Apr 1 2016

Fingerprint

Rhinovirus
Gene Expression Profiling
Inpatients
Healthy Volunteers
Outpatients
Infection
Adaptive Immunity
Virus Diseases
Innate Immunity
Respiratory Tract Infections
Cluster Analysis
Real-Time Polymerase Chain Reaction
Age Groups
RNA
Genes

Keywords

  • Asymptomatic
  • Children
  • Rhinovirus
  • Transcriptional profiling
  • Viral detection

ASJC Scopus subject areas

  • Medicine(all)
  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Rhinovirus detection in symptomatic and asymptomatic children value of host transcriptome analysis. / Heinonen, Santtu; Jartti, Tuomas; Garcia, Carla; Oliva, Silvia; Smitherman, Cynthia; Anguiano, Esperanza; De Steenhuijsen Piters, Wouter A A; Vuorinen, Tytti; Ruuskanen, Olli; Dimo, Blerta; Suarez, Nicolas M.; Pascual, Virginia; Ramilo, Octavio; Mejias, Asuncion.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 193, No. 7, 01.04.2016, p. 772-782.

Research output: Contribution to journalArticle

Heinonen, S, Jartti, T, Garcia, C, Oliva, S, Smitherman, C, Anguiano, E, De Steenhuijsen Piters, WAA, Vuorinen, T, Ruuskanen, O, Dimo, B, Suarez, NM, Pascual, V, Ramilo, O & Mejias, A 2016, 'Rhinovirus detection in symptomatic and asymptomatic children value of host transcriptome analysis', American Journal of Respiratory and Critical Care Medicine, vol. 193, no. 7, pp. 772-782. https://doi.org/10.1164/rccm.201504-0749OC
Heinonen, Santtu ; Jartti, Tuomas ; Garcia, Carla ; Oliva, Silvia ; Smitherman, Cynthia ; Anguiano, Esperanza ; De Steenhuijsen Piters, Wouter A A ; Vuorinen, Tytti ; Ruuskanen, Olli ; Dimo, Blerta ; Suarez, Nicolas M. ; Pascual, Virginia ; Ramilo, Octavio ; Mejias, Asuncion. / Rhinovirus detection in symptomatic and asymptomatic children value of host transcriptome analysis. In: American Journal of Respiratory and Critical Care Medicine. 2016 ; Vol. 193, No. 7. pp. 772-782.
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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{\%}ofasymptomatic RV1subjects, andthesecond comprised98{\%} 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.",
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AU - Heinonen, Santtu

AU - Jartti, Tuomas

AU - Garcia, Carla

AU - Oliva, Silvia

AU - Smitherman, Cynthia

AU - Anguiano, Esperanza

AU - De Steenhuijsen Piters, Wouter A A

AU - Vuorinen, Tytti

AU - Ruuskanen, Olli

AU - Dimo, Blerta

AU - Suarez, Nicolas M.

AU - Pascual, Virginia

AU - Ramilo, Octavio

AU - Mejias, Asuncion

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N2 - 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%ofasymptomatic RV1subjects, andthesecond comprised98% 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.

AB - 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%ofasymptomatic RV1subjects, andthesecond comprised98% 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.

KW - Asymptomatic

KW - Children

KW - Rhinovirus

KW - Transcriptional profiling

KW - Viral detection

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