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Differential interferon gene expression in bronchiolitis caused by respiratory syncytial virus-A genotype ON1

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Abstract

Bronchiolitis severity is determined by a complex interaction among viral replication and antiviral immunity. The current respiratory syncytial virus (RSV)-A, genotype ON1 demonstrated a high replicative capacity but seemed to be clinically less severe than the previously circulating RSV-A, NA1. To learn insights about ON1 innate immune response, we analyzed expression levels of type I/III interferon (IFN)-related genes in the respiratory mucosa of infants with RSV bronchiolitis. We enrolled RSV-positive bronchiolitis patients over 12 epidemic seasons at a university hospital in Rome. From nasopharyngeal washings’ cells (46 positive to NA1, 47 to ON1 and 28 to RSV-B, genotype BA), the mRNA copy number of the type III IFN receptor (IFNLR1 and IL10RB subunits), and of the type I/III IFN-stimulated genes, MxA and ISG56, was calculated using the threshold cycle relative quantification method with respect to an invariant gene. Expression levels of type III IFN receptor subunits genes positively correlated to each other and did not differ in infants infected with different RSV genotypes. The ISGs levels also positively correlated between them but differed among groups. MxA levels were significantly higher in NA1-infected infants than in those with ON1 and BA; ISG56 expression was slightly higher in NA1 than in the other strains. Interestingly, a moderate negative correlation existed between viral load and both ISGs values in ON1-infected infants only. The reduced ISG levels elicited during infections with ON1 (and BA) may cause a weaker control of RSV replication and/or an inadequate host immune response which may impact the risk of respiratory sequelae.

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Acknowledgements

We are grateful to all the clinical teams at the Umberto I Hospital (Sapienza University of Rome) for their contribution in the management of infants hospitalized for bronchiolitis.

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Author notes

  1. Alessandra Pierangeli and Agnese Viscido contributed equally to the study.

Authors and Affiliations

  1. Virology Laboratory, Department of Molecular Medicine, Affiliated to Pasteur Institute Italy, Cenci Bolognetti Foundation, Viale di Porta Tiburtina, 28, 00185, Rome, Italy

    Alessandra Pierangeli, Agnese Viscido, Camilla Bitossi, Federica Frasca, Massimo Gentile, Giuseppe Oliveto & Carolina Scagnolari

  2. Department of Pediatrics, “Sapienza” University, Rome, Italy

    Antonella Frassanito, Raffaella Nenna & Fabio Midulla

Authors
  1. Alessandra Pierangeli
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  2. Agnese Viscido
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  3. Camilla Bitossi
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  4. Federica Frasca
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  9. Fabio Midulla
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  10. Carolina Scagnolari
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Correspondence to Alessandra Pierangeli.

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The authors declare that they have no conflict of interest.

Ethical approval

The Sapienza University Hospital research and ethics committee approved the study. Informed consent was obtained from parents or guardians of all infants. The research was conducted in accordance with the 1964 Helsinki Declaration and its later amendments.

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Edited by Matthias J. Reddehase.

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Pierangeli, A., Viscido, A., Bitossi, C. et al. Differential interferon gene expression in bronchiolitis caused by respiratory syncytial virus-A genotype ON1. Med Microbiol Immunol 209, 23–28 (2020). https://doi.org/10.1007/s00430-019-00633-6

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