Identification of functional pathways and potential genes associated with interferon signaling during human adenovirus type 7 infection by weighted gene coexpression network analysis

作者全名："Yang, Zhongying; Wei, Jianhua; He, Yu; Ren, Luo; Chen, Shiyi; Deng, Yu; Zang, Na; Liu, Enmei"

作者地址："[Yang, Zhongying; Wei, Jianhua; He, Yu; Ren, Luo; Chen, Shiyi; Deng, Yu; Zang, Na; Liu, Enmei] Chongqing Med Univ, Chongqing Key Lab Child Infect Immun, Natl Clin Res Ctr Child Hlth & Disorders, Dept Resp,Childrens Hosp,Minist Educ,Key Lab Child, Chongqing 400014, Peoples R China"

通信作者："Zang, N (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Child Infect Immun, Natl Clin Res Ctr Child Hlth & Disorders, Dept Resp,Childrens Hosp,Minist Educ,Key Lab Child, Chongqing 400014, Peoples R China."

来源：ARCHIVES OF VIROLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:000963827800001

JCR分区：Q3

影响因子：2.7

年份：2023

卷号：168

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：Human adenovirus type 7; Coexpression network; Weighted gene coexpression network analysis (WGCNA); Pathogenesis

摘要："Human adenovirus type 7 (HAdV-7) can cause severe pneumonia and complications in children. However, the mechanism of pathogenesis and the genes involved remain largely unknown. We collected HAdV-7-infected and mock-infected A549 cells at 24, 48, and 72 hours postinfection (hpi) for RNA sequencing (RNA-Seq) and identified potential genes and functional pathways associated with HAdV-7 infection using weighted gene coexpression network analysis (WGCNA). Based on bioinformatics analysis, 12 coexpression modules were constructed by WGCNA, with the blue, tan, and brown modules significantly positively correlated with adenovirus infection at 24, 48, and 72 hpi, respectively. Functional enrichment analysis indicated that the blue module was mainly enriched in DNA replication and viral processes, the tan module was largely enriched in metabolic pathways and regulation of superoxide radical removal, and the brown module was predominantly enriched in regulation of cell death. qPCR was used to determine transcript abundance of some identified hub genes, and the 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 use as biomarkers or drug targets in HAdV-7 infection. We propose a multi-target inhibition of the interferon signaling mechanism to explain the association of HAdV-7 infection with the severity of clinical consequences. This study has allowed us to construct a framework of coexpression gene modules in A549 cells infected with HAdV-7, thus providing a basis for identifying potential genes and pathways involved in adenovirus infection and for investigating the pathogenesis of adenovirus-associated diseases."

基金机构：National Natural Science Foundation of China [32071123]; General Project of Chongqing Science and Technology Commission [cstc2020jcyj-msxmX0239]; Millions Talent Projects of Chongqing (Chongqing Commission) [187]

基金资助正文："This work was supported by the National Natural Science Foundation of China (no. 32071123), the General Project of Chongqing Science and Technology Commission (cstc2020jcyj-msxmX0239), and the Millions Talent Projects of Chongqing (Chongqing Commission [2018], NO 187)."