title: A systems biology analysis of the changes in gene expression via silencing of HPV-18 E1 expression in HeLa cells.
abstract: Previous studies have reported the detection of a truncated E1 mRNA generated from HPV-18 in HeLa cells. Although it is unclear whether a truncated E1 protein could function as a replicative helicase for viral replication, it would still retain binding sites for potential interactions with different host cell proteins. Furthermore, in this study, we found evidence in support of expression of full-length HPV-18 E1 mRNA in HeLa cells. To determine whether interactions between E1 and cellular proteins play an important role in cellular processes other than viral replication, genome-wide expression profiles of HPV-18 positive HeLa cells were compared before and after the siRNA knockdown of E1 expression. Differential expression and gene set enrichment analysis uncovered four functionally related sets of genes implicated in host defence mechanisms against viral infection. These included the toll-like receptor, interferon and apoptosis pathways, along with the antiviral interferon-stimulated gene set. In addition, we found that the transcriptional coactivator E1A-binding protein p300 (EP300) was downregulated, which is interesting given that EP300 is thought to be required for the transcription of HPV-18 genes in HeLa cells. The observed changes in gene expression produced via the silencing of HPV-18 E1 expression in HeLa cells indicate that in addition to its well-known role in viral replication, the E1 protein may also play an important role in mitigating the host's ability to defend against viral infection.
authors.affiliation: Department of Physiology and The Basic Sciences School, Health Faculty at Universidad del Valle, Cali, Colombia UniValle-Georgia Tech Genome Research Center, Health Faculty at Universidad del Valle, Cali, Colombia Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan Division of Oncogenic and Persistent Viruses, Center for Chronic Viral Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan acastillo.doc@gmail.com.
authors.forename: Andres
authors.initials: A
authors.lastname: Castillo
authors.affiliation: UniValle-Georgia Tech Genome Research Center, Health Faculty at Universidad del Valle, Cali, Colombia School of Biology, Georgia Institute of Technology, Atlanta, GA, USA PanAmerican Bioinformatics Institute, Santa Marta, Magdalena, Colombia.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Chihaya
authors.initials: C
authors.lastname: Koriyama
authors.affiliation: Division of Oncogenic and Persistent Viruses, Center for Chronic Viral Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Eizuru
authors.affiliation: UniValle-Georgia Tech Genome Research Center, Health Faculty at Universidad del Valle, Cali, Colombia School of Biology, Georgia Institute of Technology, Atlanta, GA, USA PanAmerican Bioinformatics Institute, Santa Marta, Magdalena, Colombia.
authors.forename: King
authors.initials: K
authors.lastname: Jordan
authors.affiliation: Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Suminori
authors.initials: S
authors.lastname: Akiba
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D006367:HeLa Cells; D052161:Human papillomavirus 18 / Q000378:metabolism*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D017423:Sequence Analysis, RNA; D049490:Systems Biology / Q000379:methods*; D015533:Transcriptional Activation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000821:virology
chemical_list: D009856:Oncogene Proteins, Viral; D034741:RNA, Small Interfering; C084762:oncogene protein E1, Human papillomavirus type 18
keywords: EP300 protein; HPV E1 protein; HeLa cells; human papillomavirus; microarrays analysis; siRNAs