Identifying the functional pathways and potential genes associated with interferon signaling during human adenovirus type 7 by weighted gene co-expression network analysis

Abstract

Abstract Human adenovirus type 7 (HAdV-7) can cause severe pneumonia and complications in children. However, the pathogenesis and genes involved remain largely unknown. We collected HAdV-7 infected and mock-infected A549 cells at 24, 48, and 72 hours post-infection (hpi) for RNA sequencing (RNA-seq), and identified potential genes and functional pathways associated with HAdV-7 infection using weighted gene co-expression network analysis (WGCNA).Based on bioinformatics analysis, 12 co-expression modules were constructed by WGCNA, with the blue, tan, and brown modules significantly positively correlated with Ad-24 hpi, Ad-48 hpi, and Ad-72 hpi, respectively. Functional enrichment analysis indicated that the blue module was mainly enriched in DNA replication and viral process; the tan module was largely enriched in metabolic pathways and regulation of superoxide radical removal; and the brown module was predominantly enriched regulation of cell death. qPCR was used to determine transcript abundance of some identified hub genes, and results were consistent with those from RNA-seq. Comprehensively analyzing hub genes and differentially expressed genes in the GSE68004 dataset, we identified SOCS3, OASL, ISG15, and IFIT1 as potential candidate genes for biomarkers or drug targeting in HAdV-7 infection. Further, we propose a multi-target inhibition of interferon signaling mechanism to explain the HAdV-7 associated with higher severity of clinical consequences. Overall, we constructed a framework of co-expression gene modules from A549 cells infected with HAdV-7, thus providing a basis for identifying potential genes and pathways involved in adenovirus infection and for studying the pathogenesis of adenoviruses.