title: Genetic analysis of the human papillomavirus type 31 differentiation-dependent late promoter.
abstract: Human papillomaviruses infect stratifying squamous epithelia, causing benign and malignant lesions. Upon differentiation of the host keratinocyte, the virus undergoes a dramatic increase in both DNA replication and transcription from the late promoter, leading to expression of late genes and virion morphogenesis. In human papillomavirus type 31 (HPV31), the late promoter is designated p742 and includes multiple start sites embedded within the E7 gene. In this report, we mapped viral DNA elements that control transcriptional activity from p742. Enhancer elements in the viral upstream regulatory region positively regulate this promoter. The region containing the transcriptional start sites is dispensable for activity, and at least two separate elements in the E6/E7 region are capable of supporting transcription. Of these, we mapped one to a 150-bp region of the E7 open reading frame and designate it the core p742 promoter. Using GF109203X, an inhibitor of protein kinase C signaling, we show that p742 activation is independent of viral genome amplification. Finally, we mapped elements in the region of p742 that confer responsiveness to differentiation and show that the upstream regulatory region does not contribute to the differentiation response of p742. These studies are an important step toward understanding the functioning and regulation of this multiple-start promoter.
authors.affiliation: Department of Microbiology and Immunology H107, P. O. Box 850, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Bodily
authors.forename: Craig
authors.initials: C
authors.lastname: Meyers
mesh_terms: D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D027383:Papillomaviridae / Q000235:genetics* / Q000502:physiology; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D015678:Viral Structural Proteins / Q000235:genetics; D014779:Virus Replication
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D015678:Viral Structural Proteins; D011493:Protein Kinase C; C070515:bisindolylmaleimide I
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