title: Human cytomegalovirus infection promotes the stemness of U251 glioma cells.
abstract: Glioblastoma (GBM) are the most common and aggressive tumors of human brain. Recent studies showed that human cytomegalovirus (HCMV) can induce malignant transformation of tumor cells to maintain stemness. Transcription factor 5 (ATF5) is an anti-apoptotic protein that is highly expressed in malignant glioma. The aim of this study is to investigate the effect of HCMV infection on the stem cell makers of U251 cells. U251 cells were infected by AD169 HCMV strain (MOI = 1). The expression of stem cell makers (CD133, NES, Notch1) in infected U251 cells were compared with the expression in uninfected U251 cell to see the difference between them. Then, the changes of cell proliferation activity and the expression level of Notch intracellular domain (NICD), Notch1, ATF5, and IE protein were detected in the infected cells, and the expressions of Notch1 and NICD were increased. Cell proliferation assay showed that HCMV infection significantly increased the proliferation. These cells could form tumor spheres in non-adherent conditions. Consistent with these findings, the effect of silencing ATF5 on the proliferation of HCMV-infected U251 cells was also examined. The result shows that short interfering RNA-mediated ATF5 downregulation inhibited this process. These findings imply that HCMV infection may regulate ATF5 signaling pathway to increase cell malignant traits and maintain stemness. J. Med. Virol. 89:878-886, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Microbiology, Qingdao University Medical College, Qingdao, Shandong, P.R. China.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Qingdao University Medical College, Qingdao, Shandong, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Microbiology, Qingdao University Medical College, Qingdao, Shandong, P.R. China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Xing
authors.affiliation: Department of Microbiology, Qingdao University Medical College, Qingdao, Shandong, P.R. China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Qingdao University Medical College, Qingdao, Shandong, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Qingdao University Medical College, Qingdao, Shandong, P.R. China.
authors.forename: Dongmeng
authors.initials: D
authors.lastname: Qian
mesh_terms: D000071916:AC133 Antigen / Q000032:analysis*; D051696:Activating Transcription Factors / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D003587:Cytomegalovirus / Q000254:growth & development*; D020869:Gene Expression Profiling; D006801:Humans; D064231:Nestin / Q000032:analysis*; D009457:Neuroglia / Q000821:virology*; D051881:Receptor, Notch1 / Q000032:analysis*
chemical_list: D000071916:AC133 Antigen; C507532:ATF5 protein, human; D051696:Activating Transcription Factors; C577484:NES protein, human; C497761:NOTCH1 protein, human; D064231:Nestin; C000606023:PROM1 protein, human; D051881:Receptor, Notch1
keywords: cancer stem cell; glioma; human cytomegalovirus (HCMV); transcription factor 5