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.
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.
Karstensen
Bernd
B
Sektion Experimentelle Virologie, Institut für Medizinische Virologie und Epidemiologie der Viruskrankheiten, Universitaetsklinikum Tuebingen, Elfriede-Aulhorn-Str. 6; 72076 Tuebingen, Germany.
Poppelreuther
Sven
S
Bonin
Michael
M
Walter
Michael
M
Iftner
Thomas
T
Stubenrauch
Frank
F
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
D050684:E2F Transcription Factors; D007372:Interferons