Current Issues in Molecular Biology (Feb 2023)

Expressions of Type I and III Interferons, Endogenous Retroviruses, TRIM28, and SETDB1 in Children with Respiratory Syncytial Virus Bronchiolitis

  • Pier-Angelo Tovo,
  • Silvia Garazzino,
  • Francesco Savino,
  • Valentina Daprà,
  • Giulia Pruccoli,
  • Maddalena Dini,
  • Giacomo Filisetti,
  • Elisa Funiciello,
  • Ilaria Galliano,
  • Massimiliano Bergallo

DOI
https://doi.org/10.3390/cimb45020079
Journal volume & issue
Vol. 45, no. 2
pp. 1197 – 1217

Abstract

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Interferons (IFNs) and IFN-stimulated genes (ISGs) play essential roles for the control of viral infections. Their expression in infants with respiratory syncytial virus (RSV) bronchiolitis is poorly defined. Human endogenous retroviruses (HERVs) represent 8% of our genome and modulate inflammatory and immune reactions. TRIM28 and SETDB1 participate in the epigenetic regulation of genes involved in the immune response, including IFNs and HERVs. No study has explored the expression of HERVs, TRIM28, and SETDB1 during RSV bronchiolitis. We assessed, through a PCR real-time Taqman amplification assay, the transcription levels of six IFN-I ISGs, four IFNλs, the pol genes of HERV-H, -K, and -W families, the env genes of Syncytin (SYN)1 and SYN2, and of TRIM28/SETDB1 in whole blood from 37 children hospitalized for severe RSV bronchiolitis and in healthy children (HC). The expression of most IFN-I ISGs was significantly higher in RSV+ patients than in age-matched HC, but it was inhibited by steroid therapy. The mRNA concentrations of IFN-λs were comparable between patients and age-matched HC. This lack of RSV-driven IFN-III activation may result in the defective protection of the airway mucosal surface leading to severe bronchiolitis. The expression of IFN-III showed a positive correlation with age in HC, that could account for the high susceptibility of young children to viral respiratory tract infections. The transcription levels of every HERV gene were significantly lower in RSV+ patients than in HC, while the expressions of TRIM28/SETDB1 were overlapping. Given the negative impact of HERVs and the positive effects of TRIM28/SETDB1 on innate and adaptive immune responses, the downregulation of the former and the normal expression of the latter may contribute to preserving immune functions against infection.

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