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Respiratory virome profiles reflect antiviral immune responses
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  • Judit Rovira Rubió,
  • Spyridon Megremis,
  • Maria Pasioti,
  • John Lakoumentas,
  • Bede Constantinides,
  • PARASKEVI XEPAPADAKI,
  • Claus Bachert,
  • Susetta Finotto,
  • Tuomas Jartti,
  • Evangelos Andreakos,
  • Barbara Stanic,
  • Cezmi Akdis,
  • Mubeccel Akdis,
  • Nikolaos Papadopoulos
Judit Rovira Rubió
The University of Manchester

Corresponding Author:[email protected]

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Spyridon Megremis
The University of Manchester
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Maria Pasioti
Ethniko kai Kapodistriako Panepistemio Athenon Tmema Biologias
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John Lakoumentas
Ethniko kai Kapodistriako Panepistemio Athenon Tmema Biologias
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Bede Constantinides
University of Oxford
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PARASKEVI XEPAPADAKI
Ethniko kai Kapodistriako Panepistemio Athenon Tmema Biologias
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Claus Bachert
Universiteit Gent
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Susetta Finotto
Friedrich-Alexander-Universitat Erlangen-Nurnberg
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Tuomas Jartti
Turun yliopisto
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Evangelos Andreakos
Idryma Iatrobiologikon Ereunon tes Akademias Athenon
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Barbara Stanic
Universitat Zurich Schweizerisches Institut fur Allergie- und Asthmaforschung
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Cezmi Akdis
Universitat Zurich Schweizerisches Institut fur Allergie- und Asthmaforschung
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Mubeccel Akdis
Universitat Zurich Schweizerisches Institut fur Allergie- und Asthmaforschung
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Nikolaos Papadopoulos
The University of Manchester
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Abstract

Background: From early life, respiratory viruses are implicated in the development, exacerbation and persistence of respiratory conditions such as asthma. Complex dynamics between microbial communities and host immune responses, shape immune maturation and homeostasis, influencing health outcomes. We evaluated the hypothesis that the respiratory virome is linked to systemic immune responses, using peripheral blood and nasopharyngeal swab samples from preschool-age children in the PreDicta cohort. Methods: Peripheral blood mononuclear cells from 51 children (32 asthmatics, 19 healthy controls), participating in the 2-year multinational PreDicta cohort were cultured with bacterial (Bacterial-DNA, LPS) or viral (R848, Poly:IC, RV) stimuli. Supernatants were analyzed by Luminex for the presence of 22 relevant cytokines. Virome composition was obtained using untargeted high troughput sequencing of nasopharyngeal samples. The metagenomic data were used for the characterization of virome profiles and the presence of key viral families (Picornaviridae, Anelloviridae, Siphoviridae). These were correlated to cytokine secretion patterns, identified through hierarchical clustering and principal component analysis. Results: High spontaneous cytokine release was associated with increased presence of Prokaryotic virome profiles and reduced presence of Eukaryotic and Anellovirus profiles. Antibacterial responses did not correlate with specific viral families or virome profile, however, low antiviral responders had more Prokaryotic and less Eukaryotic virome profiles. Anelloviruses and Anellovirus-dominated profiles were equally distributed amongst immune response clusters. The presence of Picornaviridae and Siphoviridae was associated with low interferon-λ responses. Asthma or allergy did not modify these correlations. Conclusions: Antiviral cytokines responses at a systemic level reflect the upper airway virome composition. Individuals with low innate interferon responses have higher abundance of Picornaviruses (mostly Rhinoviruses) and bacteriophages. Bacteriophages, particularly Siphoviridae appear to be sensitive sensors of host antimicrobial capacity, while Anelloviruses are not affected by TLR-induced immune responses.
28 Jul 2022Submitted to Allergy
03 Aug 2022Submission Checks Completed
03 Aug 2022Assigned to Editor
04 Aug 2022Reviewer(s) Assigned
20 Aug 2022Review(s) Completed, Editorial Evaluation Pending
22 Aug 2022Editorial Decision: Revise Minor
02 Dec 20221st Revision Received
02 Dec 2022Submission Checks Completed
02 Dec 2022Assigned to Editor
02 Dec 2022Review(s) Completed, Editorial Evaluation Pending
06 Dec 2022Reviewer(s) Assigned
12 Dec 2022Editorial Decision: Accept
17 Jan 2023Published in Allergy. 10.1111/all.15634