A Pilot Study on DNA Methylation in Pediatric HAdV-7-induced Sepsis

Abstract

Human adenovirus (HAdV) is one of the most common respiratory pathogens affecting children. HAdV infection has high morbidity and mortality, and it may lead to severe complications and long-term pulmonary sequelae. However, the pathogenesis of pediatric HAdV-7-induced sepsis remains unclear. The analysis of DNA methylation profiles in peripheral blood is attracting increasing attention as an effective method for investigating the pathogenesis of various diseases and identifying biomarkers of disease progression. Here, we performed reduced representation bisulfite sequencing to analyze DNA methylation in peripheral blood samples collected from 11 children with HAdV-7-induced sepsis and 5 healthy children. The Metilene software was used to analyze differential methylation in the two groups. We also performed functional enrichment analysis of the genes with differentially methylated regions (DMRs). We detected 1,138 DMRs between the two groups. Additionally, 122 DMRs were detected between the HAdV-7-induced sepsis survivor and non-survivor groups. After screening based on biological and clinical significance, we found that a group of genes (KCNQ1OT1, KPNB1, GRB10, HOXA5, HOXA4, and BCL9L) with differential methylation played an essential role in Wnt signaling. Additionally, genes related to the Wnt/β-catenin signaling pathway, such as MEG3, GNAS-AS1, and GNAS, exhibited differential methylation in the survivor and non-survivor groups. Our data suggest that specific patterns of DNA methylation are associated with the occurrence and progression of HAdV-7-induced sepsis. Wnt signaling was also affected by the changes in methylation. Thus, we identified potential biomarkers and therapeutic targets for pediatric HAdV-7-induced sepsis.