Cervical lesions are associated with human papillomavirus type 16 intratypic variants that have high transcriptional activity and increased usage of common mammalian codons

• Published in: Journal of general virology 2000-06, Vol.81 (6), p.1517-1527
• Main Authors: Bible, Jon M, Mant, Christine, Best, Jennifer M, Kell, Barbara, Starkey, William G, Shanti Raju, K, Seed, Paul, Biswas, Chandrima, Muir, Peter, Banatvala, Jangu E, Cason, John
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Cervical Intraepithelial Neoplasia - pathology; Cervical Intraepithelial Neoplasia - virology; Cervix Uteri - pathology; Cervix Uteri - virology; Codon; DNA, Viral; Female; Genetic Variation; Human papillomavirus 16; Humans; Molecular Sequence Data; Oncogene Proteins, Viral - genetics; Papillomaviridae - genetics; Papillomavirus Infections - pathology; Papillomavirus Infections - virology; Transcription, Genetic; Tumor Virus Infections - pathology; Tumor Virus Infections - virology; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-81-6-1517

The Richard Dimbleby Laboratory of Cancer Virology 1 and the Departments of Infection 2 , Obstetrics and Gynaecology 3 and Public Health Medicine 4 , Guy’s, King’s College and St Thomas’ Medical and Dental Schools, King’s College London, St Thomas’ Campus, Lambeth Palace Road, London SE1 7EH, UK Author for correspondence: John Cason. Fax [phone]. e-mail jwcason{at}AOL.com 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.