title: Phylogenetic and functional analysis of sequence variation of human papillomavirus type 31 E6 and E7 oncoproteins.
abstract: High-risk human papillomaviruses (HPV) are the causative agents of cervical and other anogenital cancers as well as a subset of head and neck cancers. The E6 and E7 oncoproteins of HPV contribute to oncogenesis by associating with the tumour suppressor protein p53 and pRb, respectively. For HPV types 16 and 18, intratypic sequence variation was shown to have biological and clinical significance. The functional significance of sequence variation among HPV 31 variants was studied less intensively. HPV 31 variants belonging to different variant lineages were found to have differences in persistence and in the ability to cause high grade cervical intraepithelial neoplasia. In the present study, we started to explore the functional effects of natural sequence variation of HPV 31 E6 and E7 oncoproteins. The E6 variants were tested for their effects on p53 protein stability and transcriptional activity, while the E7 variants were tested for their effects on pRb protein level and also on the transcriptional activity of E2F transcription factors. HPV 31 E7 variants displayed uniform effects on pRb stability and also on the activity of E2F transcription factors. HPV 31 E6 variants had remarkable differences in the ability to inhibit the trans-activation function of p53 but not in the ability to induce the in vivo degradation of p53. Our results indicate that natural sequence variation of the HPV 31 E6 protein may be involved in the observed differences in the oncogenic potential between HPV 31 variants.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
authors.forename: Annamária
authors.initials: A
authors.lastname: Ferenczi
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Gyöngyösi
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
authors.forename: Anita
authors.initials: A
authors.lastname: Szalmás
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
authors.forename: Brigitta
authors.initials: B
authors.lastname: László
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Kónya
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. Electronic address: veregy@med.unideb.hu.
authors.forename: György
authors.initials: G
authors.lastname: Veress
mesh_terms: D050684:E2F Transcription Factors / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D058952:Human papillomavirus 31 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000821:virology*; D010802:Phylogeny; D055550:Protein Stability; D056286:Retinoblastoma Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D050684:E2F Transcription Factors; C572886:E6 protein, Human papillomavirus type 31; C502189:E7 protein, Human papillomavirus type 31; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases
keywords: E6; E7; Functional analysis; Human papillomavirus; Type 31; Variants