title: Cervical lesions are associated with human papillomavirus type 16 intratypic variants that have high transcriptional activity and increased usage of common mammalian codons.
abstract: Human papillomavirus type 16 (HPV-16) is a major cause of cervical neoplasia, but only a minority of HPV-16 infections result in cancer. Whether particular HPV-16 variants are associated with cervical disease has not yet been clearly established. An investigation of whether cervical neoplasia is associated with infection with HPV-16 intratypic variants was undertaken by using RFLP analyses in a study of 100 HPV-16 DNA-positive women with or without neoplasia. RFLP variant 2 was positively associated [odds ratio (OR)=2.57] and variant 5 was negatively associated with disease (OR=0.2). Variant 1, which resembles the reference isolate of HPV-16, was found at a similar prevalence among those with and without neoplasia. Variants 1 and 2 were also more likely to be associated with detectable viral mRNA than variant 5 (respectively P=0.03 and P=0.00). When HPV-16 E5 ORFs in 50 clones from 36 clinical samples were sequenced, 19 variant HPV-16 E5 DNA sequences were identified. Twelve of these DNA sequences encoded variant E5 amino acid sequences, 10 of which were novel. Whilst the associations between HPV-16 E5 RFLP variants and neoplasia could not be attributed to differences in amino acid sequences, correlation was observed in codon usage. DNA sequences of RFLP variant 2 (associated with greatest OR for neoplasia) had a significantly greater usage of common mammalian codons compared with RFLP pattern 1 variants.
authors.affiliation: The Richard Dimbleby Laboratory of Cancer Virology, Guy's, King's College and St Thomas' Medical and Dental Schools, King's College London, St Thomas' Campus, London, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Bible
authors.forename: C
authors.initials: C
authors.lastname: Mant
authors.forename: J M
authors.initials: JM
authors.lastname: Best
authors.forename: B
authors.initials: B
authors.lastname: Kell
authors.forename: W G
authors.initials: WG
authors.lastname: Starkey
authors.forename: K
authors.initials: K
authors.lastname: Shanti Raju
authors.forename: P
authors.initials: P
authors.lastname: Seed
authors.forename: C
authors.initials: C
authors.lastname: Biswas
authors.forename: P
authors.initials: P
authors.lastname: Muir
authors.forename: J E
authors.initials: JE
authors.lastname: Banatvala
authors.forename: J
authors.initials: J
authors.lastname: Cason
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology*; D003062:Codon; D004279:DNA, Viral; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology*; D014158:Transcription, Genetic; D014412:Tumor Virus Infections / Q000473:pathology / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*; D000086082:Viroporin Proteins
chemical_list: D003062:Codon; D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins