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Using integrated omics to assess the effects of rhinovirus infection in children with Cystic Fibrosis (CF)

Patricia Agudelo-Romero, Kelly Martinovich, Joshua D Chandler, Kak-Ming Ling, Erika N Sutanto, Dean P Jones, Rabindra M Tirouvanzium, Stephen M Stick, Luke W Garratt, Anthony Kicic, Wa Erp, Arest Cf
European Respiratory Journal 2020 56: 4342; DOI: 10.1183/13993003.congress-2020.4342
Patricia Agudelo-Romero
1Telethon Kids Institute, Perth (WA), Australia
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  • For correspondence: Patricia.AgudeloRomero@telethonkids.org.au
Kelly Martinovich
2Telethon Kids Institute; Murdoch University, Perth (WA), Australia
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Joshua D Chandler
3Emory University, School of Medicine, Atlanta (GA), United States of America
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Kak-Ming Ling
1Telethon Kids Institute, Perth (WA), Australia
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Erika N Sutanto
1Telethon Kids Institute, Perth (WA), Australia
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Dean P Jones
3Emory University, School of Medicine, Atlanta (GA), United States of America
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Rabindra M Tirouvanzium
4Emory University, Department of Pediatrics, Atlanta (GA), United States of America
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Stephen M Stick
5Telethon Kids Institute; Faculty of Health and Medical Science, University of Western Australia; Department of Respiratory and Sleep Medicine, Perth Children’s Hospital for Children, WA;Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, UWA., Perth (WA), Australia
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Luke W Garratt
1Telethon Kids Institute, Perth (WA), Australia
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Anthony Kicic
6Telethon Kids Institute; Faculty of Health and Medical Science, University of Western Australia;Department of Respiratory and Sleep Medicine, Perth Children’s Hospital for Children, WA;Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, UWA;School of Public Health, Curtin University, WA., Perth (WA), Australia
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Wa Erp
1Telethon Kids Institute, Perth (WA), Australia
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Arest Cf
7Telethon Kids Institute;Murdoch Children’s Research Institute; Department of Respiratory and Sleep Medicine, Perth Children’s Hospital for Children, WA; Department of Respiratory and Sleep Medicine, Perth Children’s Hospital for Children, WA; Department of Respiratory Medicine, Royal Children’s Hospital, WA., Perth (WA), Australia
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Abstract

Introduction/Aim: Children with Cystic Fibrosis (CF) typically exhibit prolonged and severe symptoms during rhinovirus (RV) infection compared to healthy children. Here, we studied the host-rhinovirus interaction signature after infection, integrating two omics: (1) Whole transcriptome sequencing (WTS) to determine the viral load and host’s gene expression, and (2) metabolomics to profile the metabolites associated with the viral infection of primary tracheal epithelial cells obtained from healthy children (H) and those with CF.

Methods: WTS and hydrophilic interaction liquid chromatography (HILIC) coupled to mass spectrometry, were used to identify the differences in transcripts/metabolites and RV coverage produced by H (3.9 ± 1.5 years; n=8) and CF (2.6 ± 1.8 years; n=8; all p.Phe508del/p.Phe508del) primary epithelial cells at 24 hours post-infection with human rhinovirus 1B. Univariate and multivariate analyses were then performed to identify the infection hallmark.

Results: RV coverage in uninfected cells (Mock) was less than 0.5X, whereas, infected cells presented 44.4X and 101.6X of RV in children with and without CF respectively. Global RV infection was associated with 14 metabolites and 1713 genes differential expressed. From these, several metabolic pathways were found dysregulated including inositol metabolism and glycerophospholipid biosynthesis.

Conclusion: Metabolic host-derived pathways associated with RV infection were identified. Although functional analysis is still required, these pathways could be used as potential biomarkers of RV infection in CF. Future analysis will help to understand whether these compounds can be targeted for antiviral purposes.

  • Viruses
  • Children
  • Cystic fibrosis

Footnotes

Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4342.

This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2020
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Using integrated omics to assess the effects of rhinovirus infection in children with Cystic Fibrosis (CF)
Patricia Agudelo-Romero, Kelly Martinovich, Joshua D Chandler, Kak-Ming Ling, Erika N Sutanto, Dean P Jones, Rabindra M Tirouvanzium, Stephen M Stick, Luke W Garratt, Anthony Kicic, Wa Erp, Arest Cf
European Respiratory Journal Sep 2020, 56 (suppl 64) 4342; DOI: 10.1183/13993003.congress-2020.4342

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Using integrated omics to assess the effects of rhinovirus infection in children with Cystic Fibrosis (CF)
Patricia Agudelo-Romero, Kelly Martinovich, Joshua D Chandler, Kak-Ming Ling, Erika N Sutanto, Dean P Jones, Rabindra M Tirouvanzium, Stephen M Stick, Luke W Garratt, Anthony Kicic, Wa Erp, Arest Cf
European Respiratory Journal Sep 2020, 56 (suppl 64) 4342; DOI: 10.1183/13993003.congress-2020.4342
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