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COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases.
Int J Mol Sci. 2021 Jul 13; 22(14)IJ

Abstract

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. TRIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children and in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19 children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.

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Authors+Show Affiliations

Tovo PA
Department of Pediatric Sciences and Public Health, University of Turin, Piazza Polonia 94, 10126 Turin, Italy.
Garazzino S
Infectious Diseases Unit, Department of Pediatrics, Regina Margherita Children's Hospital, Piazza Polonia 94, 10126 Turin, Italy.
Daprà V
Pediatric Laboratory, Department of Pediatric Sciences and Public Health, University of Turin, 10126 Turin, Italy.
Pruccoli G
Department of Pediatric Sciences and Public Health, University of Turin, Piazza Polonia 94, 10126 Turin, Italy.
Calvi C
Department of Pediatric Sciences and Public Health, University of Turin, Piazza Polonia 94, 10126 Turin, Italy. Pediatric Laboratory, Department of Pediatric Sciences and Public Health, University of Turin, 10126 Turin, Italy.
Mignone F
Infectious Diseases Unit, Department of Pediatrics, Regina Margherita Children's Hospital, Piazza Polonia 94, 10126 Turin, Italy.
Alliaudi C
Department of Pediatric Sciences and Public Health, University of Turin, Piazza Polonia 94, 10126 Turin, Italy. Pediatric Laboratory, Department of Pediatric Sciences and Public Health, University of Turin, 10126 Turin, Italy.
Denina M
Department of Pediatric Sciences and Public Health, University of Turin, Piazza Polonia 94, 10126 Turin, Italy.
Scolfaro C
Infectious Diseases Unit, Department of Pediatrics, Regina Margherita Children's Hospital, Piazza Polonia 94, 10126 Turin, Italy.
Zoppo M
Infectious Diseases Unit, Department of Pediatrics, Regina Margherita Children's Hospital, Piazza Polonia 94, 10126 Turin, Italy.
Licciardi F
Department of Pediatric Sciences and Public Health, University of Turin, Piazza Polonia 94, 10126 Turin, Italy.
Ramenghi U
Department of Pediatric Sciences and Public Health, University of Turin, Piazza Polonia 94, 10126 Turin, Italy.
Galliano I
Department of Pediatric Sciences and Public Health, University of Turin, Piazza Polonia 94, 10126 Turin, Italy. Pediatric Laboratory, Department of Pediatric Sciences and Public Health, University of Turin, 10126 Turin, Italy.
Bergallo M
Department of Pediatric Sciences and Public Health, University of Turin, Piazza Polonia 94, 10126 Turin, Italy. Pediatric Laboratory, Department of Pediatric Sciences and Public Health, University of Turin, 10126 Turin, Italy.

MeSH

COVID-19Case-Control StudiesChildEndogenous RetrovirusesFemaleHistone-Lysine N-MethyltransferaseHumansInterferon Type IInterferon-gammaInterferonsItalyMaleSARS-CoV-2Severity of Illness IndexTripartite Motif-Containing Protein 28Interferon Lambda

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

34299101

Citation

Tovo, Pier-Angelo, et al. "COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases." International Journal of Molecular Sciences, vol. 22, no. 14, 2021.
Tovo PA, Garazzino S, Daprà V, et al. COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases. Int J Mol Sci. 2021;22(14).
Tovo, P. A., Garazzino, S., Daprà, V., Pruccoli, G., Calvi, C., Mignone, F., Alliaudi, C., Denina, M., Scolfaro, C., Zoppo, M., Licciardi, F., Ramenghi, U., Galliano, I., & Bergallo, M. (2021). COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases. International Journal of Molecular Sciences, 22(14). https://doi.org/10.3390/ijms22147481
Tovo PA, et al. COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases. Int J Mol Sci. 2021 Jul 13;22(14) PubMed PMID: 34299101.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases. AU - Tovo,Pier-Angelo, AU - Garazzino,Silvia, AU - Daprà,Valentina, AU - Pruccoli,Giulia, AU - Calvi,Cristina, AU - Mignone,Federica, AU - Alliaudi,Carla, AU - Denina,Marco, AU - Scolfaro,Carlo, AU - Zoppo,Marisa, AU - Licciardi,Francesco, AU - Ramenghi,Ugo, AU - Galliano,Ilaria, AU - Bergallo,Massimiliano, Y1 - 2021/07/13/ PY - 2021/05/28/received PY - 2021/07/07/revised PY - 2021/07/10/accepted PY - 2021/7/24/entrez PY - 2021/7/25/pubmed PY - 2021/7/31/medline KW - COVID-19 KW - SARS-CoV-2 KW - SETDB1 KW - TRIM28 KW - children KW - human endogenous retroviruses KW - interferon JF - International journal of molecular sciences JO - Int J Mol Sci VL - 22 IS - 14 N2 - Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. TRIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children and in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19 children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/34299101/COVID_19_in_Children:_Expressions_of_Type_I/II/III_Interferons_TRIM28_SETDB1_and_Endogenous_Retroviruses_in_Mild_and_Severe_Cases_ DB - PRIME DP - Unbound Medicine ER -