Preliminary Evidence of the Differential Expression of Human Endogenous Retroviruses in Kawasaki Disease and SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children

Int J Mol Sci. 2023 Oct 11;24(20):15086. doi: 10.3390/ijms242015086.

Abstract

Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some clinical features overlapping with Kawasaki disease (KD). Our research group and others have highlighted that the spike protein of SARS-CoV-2 can trigger the activation of human endogenous retroviruses (HERVs), which in turn induces inflammatory and immune reactions, suggesting HERVs as contributing factors in COVID-19 immunopathology. With the aim to identify new factors involved in the processes underlying KD and MIS-C, we analysed the transcriptional levels of HERVs, HERV-related genes, and immune mediators in children during the acute and subacute phases compared with COVID-19 paediatric patients and healthy controls. The results showed higher levels of HERV-W, HERV-K, Syn-1, and ASCT-1/2 in KD, MIS-C, and COV patients, while higher levels of Syn-2 and MFSD2A were found only in MIS-C patients. Moreover, KD and MIS-C shared the dysregulation of several inflammatory and regulatory cytokines. Interestingly, in MIS-C patients, negative correlations have been found between HERV-W and IL-10 and between Syn-2 and IL-10, while positive correlations have been found between HERV-K and IL-10. In addition, HERV-W expression positively correlated with the C-reactive protein. This pilot study supports the role of HERVs in inflammatory diseases, suggesting their interplay with the immune system in this setting. The elevated expression of Syn-2 and MFSD2A seems to be a distinctive trait of MIS-C patients, allowing to distinguish them from KD ones. The understanding of pathological mechanisms can lead to the best available treatment for these two diseases, limiting complications and serious outcomes.

Keywords: COVID-19; HERVs; Kawasaki disease; human endogenous retroviruses; inflammation; multisystem inflammatory syndrome in children.

MeSH terms

  • COVID-19* / complications
  • COVID-19* / genetics
  • Child
  • Endogenous Retroviruses* / genetics
  • Humans
  • Interleukin-10 / genetics
  • Mucocutaneous Lymph Node Syndrome* / genetics
  • Pilot Projects
  • SARS-CoV-2 / genetics
  • Systemic Inflammatory Response Syndrome

Substances

  • Interleukin-10

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related