title: Gene expression profiles reveal an upregulation of E2F and downregulation of interferon targets by HPV18 but no changes between keratinocytes with integrated or episomal viral genomes.
abstract: Persistent infections with human papillomaviruses type 18 can result in the development of cervical cancer. HPV18 genomes persist extrachromosomally in low-grade and precancerous lesions but are always integrated in cervical cancers, and this might contribute to the progression of HPV18-induced lesions. To address whether integration induces additional changes in host cells, several keratinocyte lines with wild type and replication-deficient E1 mutant HPV18 (E1C-TTL) genomes were analyzed with high density oligonucleotide arrays. In comparison to normal keratinocytes, wild type and integrated E1C-TTL HPV18 genomes deregulate the expression of 280 annotated genes. However, the comparison of wild type with E1C-TTL cell lines did not reveal any significant differences, indicating that neither the loss of E1 nor viral integration induces additional gene expression changes in low passage HPV18-positive keratinocytes. Half of the deregulated genes have been described as targets of the p16/Rb/E2F, p53, interferon or NFkappaB pathways consistent with the functions ascribed to the viral E6 and E7 oncoproteins, but the other half can currently not be ascribed to certain pathways.
authors.affiliation: Sektion Experimentelle Virologie, Institut für Medizinische Virologie und Epidemiologie der Viruskrankheiten, Universitaetsklinikum Tuebingen, Elfriede-Aulhorn-Str. 6; 72076 Tuebingen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Karstensen
authors.forename: Sven
authors.initials: S
authors.lastname: Poppelreuther
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Michael
authors.initials: M
authors.lastname: Walter
authors.forename: Thomas
authors.initials: T
authors.lastname: Iftner
authors.forename: Frank
authors.initials: F
authors.lastname: Stubenrauch
mesh_terms: D002460:Cell Line; D018920:Coculture Techniques; D015536:Down-Regulation; D050684:E2F Transcription Factors / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D052161:Human papillomavirus 18 / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000821:virology*; D008297:Male; D010957:Plasmids / Q000235:genetics*; D015854:Up-Regulation; D016662:Virus Integration
chemical_list: D050684:E2F Transcription Factors; D007372:Interferons