Genetic diversity of human papillomavirus type 16 E6, E7, and L1 genes in Italian women with different grades of cervical lesions

Cento, Valeria; Ciccozzi, Massimo; Ronga, Luigi; Perno, Carlo Federico; Ciotti, Marco

doi:10.1002/jmv.21552

Cited by 23 publications

(16 citation statements)

References 30 publications

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“…We did not find association between the presence of these mutations and the severity of the lesions, in agreement to other authors like Cento et al [25] studying Italian women and Liu et al [33] studying Chinese women. In the later study, there were reported additional changes in E7 positions such as G599A (R9K), C632T (T20I), G694A (G41R), t744g, G760A (G63S), and G761A (G63D).…”

Section: Discussionsupporting

confidence: 81%

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Genetic Variability in E6 and E7 Oncogenes from Human Papillomavirus Type 58 in Mexican Women

et al. 2017

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Background/Aims: The study aimed to describe human papillomavirus (HPV) 58 genetic variability in E6 and E7 oncogenes from women in southeast Mexico and their phylogenetic relationships with the sequences from other geographical regions. Methods: The E6-E7 region was amplified by nested PCR, and sequenced for identification of polymorphisms, phylogenetic trees construction, and haplotype and fixation tests. Results: HPV58 positive samples were obtained from a repository, 54 were amplified, 47 sequences for the E6 gene, and 51 sequences for the E7 gene were obtained. Fifteen new E6 mutations were found; the most frequent were G279T (G57V; 29.78%), T249G (F47C; 34.04%), and A270G (Y54C; 34.04%), and previously reported c307t (63.82%). For E7, 17 known mutations were found, the most frequent were C632T (T20I), 35.30%, G760A (G63S), 35.30%, and t744g 74.50%. No significant association with the severity of the lesions was found. The polytomy in the E6 tree did not allow proposing phylogenetic relationship, and E7 tree presented defined branches. All sequences were presumably A lineage, most closely related to A1 and/or A3 sublineage. HPV58 variants are not specific for a geographical area. Population and fixation analyses suggest a possible Asian origin of HPV58 from Yucatan. The most frequent E7 haplotype in Yucatan groups with other populations of the world. Conclusion: The genetic variability of HPV58 from Mexico was described for the first time. E7 was more conserved than E6. New mutants present exclusively in Yucatan were identified.

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Section: Discussionsupporting

confidence: 81%

“…More recently, the ICTV Papillomavirus Study Group proposed an entire genomic approach (for information on current HPV taxonomy, https://pave.niaid.nih.gov/index.html). Variants in the oncogenes E6/E7 genes and LCR have also been of interest for the potential association with disease [25,31,32].…”

Section: Discussionmentioning

confidence: 99%

Genetic Variability in E6 and E7 Oncogenes from Human Papillomavirus Type 58 in Mexican Women

et al. 2017

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“…Human Papillomavirus type 16 (HPV16) is the most prevalent oncogenic HPV type worldwide and the prevalence of its different lineages differs across geographical locations (zur Hausen 1991; Cento et al, 2009;Cornet et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Mutation Detection of E6 and LCR Genes from HPV 16 Associated with Carcinogenesis

Mosmann¹,

Monetti²,

Frutos³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Human papillomavirus (HPV) is responsible for one of the most frequent sexually transmitted infections. The first phylogenetic analysis was based on a LCR region fragment. Nowadays, 4 variants are known: African (Af-1, Af-2), Asian-American (AA) and European (E). However the existence of sub-lineages of the European variant havs been proposed, specific mutations in the E6 and LCR sequences being possibly related to persistent viral infections. The aim of this study was a phylogenetic study of HPV16 sequences of endocervical samples from Córdoba, in order to detect the circulating lineages and analyze the presence of mutations that could be correlated with malignant disease. The phylogenetic analysis determined that 86% of the samples belonged to the E variant, 7% to AF-1 and the remaining 7% to AF-2. The most frequent mutation in LCR sequences was G7521A, in 80% of the analyzed samples; it affects the binding site of a transcription factor that could contribute to carcinogenesis. In the E6 sequences, the most common mutation was T350G (L83V), detected in 67% of the samples, associated with increased risk of persistent infection. The high detection rate of the European lineage correlated with patterns of human migration. This study emphasizes the importance of recognizing circulating lineages, as well as the detection of mutations associated with high-grade neoplastic lesions that could be correlated to the development of carcinogenic lesions.

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“…The latter represents a single variant among 35 HPV-16 cervical cancer or cervicitis patients analyzed. Analysis of the complete E7 open reading frame from those 35 patients revealed four nucleotide variations in three (8.5%) patients, whereas the other 32 did not contain any nucleotide changes compared with the prototype (52). Of the identified changes, two were silent nucleotide changes, and two were missense substitutions, resulting in the amino acid changes L15V and S31R.…”

Section: Generation and Characterization Of T Cell Lines-tomentioning

confidence: 99%

A Conserved E7-derived Cytotoxic T Lymphocyte Epitope Expressed on Human Papillomavirus 16-transformed HLA-A2+ Epithelial Cancers

Riemer

Keskin

Zhang

et al. 2010

Journal of Biological Chemistry

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Human Papillomavirus 16 (HPV-16) has been identified as the causative agent of 50% of cervical cancers and many other HPV-associated tumors. The transforming potential/tumor maintenance capacity of this high risk HPV is mediated by two viral oncoproteins, E6 and E7, making them attractive targets for therapeutic vaccines. Of 21 E6 and E7 peptides computed to bind HLA-A*0201, 10 were confirmed through TAP-deficient T2 cell HLA stabilization assay. Those scoring positive were investigated to ascertain which were naturally processed and presented by surface HLA molecules for CTL recognition. Because IFN␥ ELISpot frequencies from healthy HPV-exposed blood donors against HLA-A*0201-binding peptides were unable to identify specificities for tumor targeting, their physical presence among peptides eluted from HPV-16-transformed epithelial tumor HLA-A*0201 immunoprecipitates was analyzed by MS 3 Poisson detection mass spectrometry. Only one epitope (E7 11-19 ) highly conserved among HPV-16 strains was detected. This 9-mer serves to direct cytolysis by T cell lines, whereas a related 10-mer (E7 11-20 ), previously used as a vaccine candidate, was neither detected by MS 3 on HPV-transformed tumor cells nor effectively recognized by 9-mer specific CTL. These data underscore the importance of precisely defining CTL epitopes on tumor cells and offer a paradigm for T cellbased vaccine design.The transforming potential of human Papillomavirus (HPV), 4 first suspected in the 1970s, has now been firmly established both biologically and epidemiologically (1-3). The single most important variable linked to malignant transformation is persistent infection with one of the high-risk HPV types. The E6 and E7 proteins encoded by high-risk HPVs have transforming activities and functionally inactivate the p53 and retinoblastoma (Rb) tumor suppressor proteins, respectively (3, 4). HPV-16 is the most abundant high risk HPV and has been detected in Ͼ50% of cervical cancer cases and in most other HPV-induced tumors, such as carcinomas of the vagina, anus, vulva, penis, and oropharynx (3, 5, 6). Worldwide, high risk HPVs are thought to be responsible for Ͼ500,000 malignancies per year, representing more than 5% of human cancers (7).A major breakthrough in combating HPV-induced disease was the development of prophylactic vaccines to prevent HPV infection in previously unexposed individuals. These vaccines are based on virus-like particles consisting of the L1 capsid protein (8, 9). Virus-like particles resemble natural virions and are able to induce high titers of L1-neutralizing antibodies. Two vaccines, one against HPV-16, -18, -6, and -11 and another against HPV-16 and -18, were approved for clinical use in 2006 (10 -12). Although the impact of prophylactic HPV vaccination on the incidence of vaccine type HPV-associated disease and cancer is unquestionable over time, these vaccines have no therapeutic efficacy for established HPV infections. Antibodies neutralize virus particles only before infection. Moreover, as HPV capsid proteins are exc...

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Genetic diversity of human papillomavirus type 16 E6, E7, and L1 genes in Italian women with different grades of cervical lesions

Cited by 23 publications

References 30 publications

Genetic Variability in E6 and E7 Oncogenes from Human Papillomavirus Type 58 in Mexican Women

Genetic Variability in E6 and E7 Oncogenes from Human Papillomavirus Type 58 in Mexican Women

Mutation Detection of E6 and LCR Genes from HPV 16 Associated with Carcinogenesis

A Conserved E7-derived Cytotoxic T Lymphocyte Epitope Expressed on Human Papillomavirus 16-transformed HLA-A2+ Epithelial Cancers

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