title: The E7 open reading frame acts in cis and in trans to mediate differentiation-dependent activities in the human papillomavirus type 16 life cycle.
abstract: Human papillomaviruses (HPVs) are the causative agents of several important genital and other mucosal cancers. The HPV16 E7 gene encodes a viral oncogene that is necessary for the continued growth of cancer cells, but its role in the normal, differentiation-dependent life cycle of the virus is not fully understood. The function of E7 in the viral life cycle was examined using a series of mutations of E7 created in the context of the complete HPV16 genome. The effect of these E7 mutations on key events of the viral life cycle, including immortalization, episomal maintenance, late promoter activation, and infectious virion synthesis, was examined. Our studies show that the pRb binding domain is indispensable for early viral activities, whereas the C-terminal zinc finger domain contributed primarily to very late events. Mutations of the casein kinase II phosphorylation site caused a complex phenotype involving both the function of E7 protein and a cis element necessary for the activation of the late promoter, identifying for the first time a promoter element important for late promoter function in the context of the viral genome. All mutant genomes tested showed reduced viral titers following growth in organotypic raft cultures. These studies clarify the role of E7 as a regulator of late events in the differentiation-dependent HPV life cycle.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Bodily
authors.forename: Kavi P M
authors.initials: KP
authors.lastname: Mehta
authors.forename: Linda
authors.initials: L
authors.lastname: Cruz
authors.forename: Craig
authors.initials: C
authors.lastname: Meyers
authors.forename: Laimonis A
authors.initials: LA
authors.lastname: Laimins
mesh_terms: D002454:Cell Differentiation; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D006801:Humans; D016366:Open Reading Frames; D050725:Papillomavirus E7 Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014779:Virus Replication
chemical_list: D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16