Department of Pediatric Sciences and Public Health, University of Turin, Piazza Polonia 94, 10126 Turin, Italy.
Infectious Diseases Unit, Department of Pediatrics, Regina Margherita Children's Hospital, Piazza Polonia 94, 10126 Turin, Italy.
Int J Mol Sci. 2021 Jul 13;22(14):7481. doi: 10.3390/ijms22147481.
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.
儿童感染 2019 年新型冠状病毒病 (COVID-19) 的症状比成人患者轻，预后较好。几项研究评估了 SARS-CoV-2 感染成人的 I、II 和 III 型干扰素 (IFN) 特征，但尚无儿科患者的数据。TRIM28 和 SETDB1 调节参与免疫反应和人类内源性逆转录病毒 (HERV) 的多个基因的转录。外源性病毒感染可触发 HERV 的激活，进而可诱导炎症和免疫反应。尽管 SARS-CoV-2 感染与 TRIM28、SETDB1 和 HERV 之间存在潜在的串扰，但关于它们在 COVID-19 患者中的表达情况的信息尚缺乏。我们通过实时 Taqman PCR 扩增测定法评估了 6 种 IFN-I 刺激基因、IFN-II 及其 3 种敏感基因、3 种 IFN-lIIs 以及 TRIM28、SETDB1、HERV-H、-K 和 -W 家族的 pol 基因和 Syncytin (SYN)1、SYN2 和多发性硬化症相关逆转录病毒 (MRSV) 的 env 基因在 COVID-19 患儿和未感染对照者的外周血中的转录水平。与未感染对照者相比，36 例轻度或中度疾病的 COVID-19 患儿 IFN-I 和 IFN-II 诱导基因的表达水平较高，而 17 例重症患儿和 11 例多系统炎症综合征 (MIS-C) 患儿的浓度降低。TRIM-28、SETDB1 和每种 HERV 基因的表达也发现了类似的结果。COVID-19 患者中 I 型和 II 型 IFNs、TRIM28、SETDB1 和 HERVs 的转录水平之间出现正相关。IFN-III 的表达在各组受试者中相似。与成人相比，IFN-III 缺乏症在成人中报道，IFN-λ 的这种诱导保存可能有助于儿童更好地控制感染。在症状较轻的儿童中，IFN-I、IFN-II、TRIM28、SETDB1 和 HERVs 的上调，在重症病例或伴有 MIS-C 的情况下下降，以及 SARS-CoV-2 感染儿童中这些基因转录的正相关，表明它们可能在调节感染的演变中发挥重要作用。
