Characterization of sequence variations within HPV16 isolates among Indian women: Prediction of causal role of rare non-synonymous variations within intact isolates in cervical cancer pathogenesis

Bhattacharjee, Bornali; Mandal, Nidhu Ranjan; Roy, Sudipta; Sengupta, Shamik

doi:10.1016/j.virol.2008.04.007

Cited by 24 publications

(55 citation statements)

References 43 publications

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“…The phylogenetic tree segregated into four major branches (i.e., lineages) that could be recognized by the nomenclature of previous studies: (i) EAS, including the European (EUR) and Asian (As) sublineages, (ii) African 1 (AFR1), including two sublineages that we tentatively defined as AFR1a and AFR1b, (iii) African 2 (AFR2), including two sublineages that we tentatively defined as AFR2a and AFR2b, and (iv) AA/NA, including the North American (NA), Asian-American-1 (AA1), and Asian-American-2 (AA2) sublineages. A second, larger, phylogenetic tree was generated including all 353 unique E6/LCR variants from the present study, as well as additional novel published E6/LCR sequences retrieved from the work of Kammer (1,15,20) (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…Our thanks to Sharmila Sengupta for sharing raw data from the 2008 paper of Bhattacharjee et al (1). Thanks also go to Sophie Pallardy, Annie Arslan, Vanessa Tenet, Sophie Guillot, Annick Rivoire, and Veronique Chabanis for technical and/or administrative support to the project and to the very many IARC and local collaborators who contributed to the epidemiological studies from which the samples for this study were sourced.…”

Section: Acknowledgmentsmentioning

confidence: 97%

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Human Papillomavirus Type 16 Genetic Variants: Phylogeny and Classification Based on E6 and LCR

Cornet

Gheit

Franceschi

et al. 2012

J Virol

145

152

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Naturally occurring genetic variants of human papillomavirus type 16 (HPV16) are common and have previously been classified into 4 major lineages; European-Asian (EAS), including the sublineages European (EUR) and Asian (As), African 1 (AFR1), African 2 (AFR2), and North-American/Asian-American (NA/AA). We aimed to improve the classification of HPV16 variant lineages by using a large resource of HPV16-positive cervical samples collected from geographically diverse populations in studies on HPV and/or cervical cancer undertaken by the International Agency for Research on Cancer. In total, we sequenced the entire E6 genes and long control regions (LCRs) of 953 HPV16 isolates from 27 different countries worldwide. Phylogenetic analyses confirmed previously described variant lineages and subclassifications. We characterized two new sublineages within each of the lineages AFR1 and AFR2 that are robustly classified using E6 and/or the LCR. We could differentiate previously identified AA1, AA2, and NA sublineages, although they could not be distinguished by E6 alone, requiring the LCR for correct phylogenetic classification. We thus provide a classification system for HPV16 genomes based on 13 and 32 phylogenetically distinguishing positions in E6 and the LCR, respectively, that distinguish nine HPV16 variant sublineages (EUR, As, AFR1a, AFR1b, AFR2a, AFR2b, NA, AA1, and AA2). Ninety-seven percent of all 953 samples fitted this classification perfectly. Other positions were frequently polymorphic within one or more lineages but did not define phylogenetic subgroups. Such a standardized classification of HPV16 variants is important for future epidemiological and biological studies of the carcinogenic potential of HPV16 variant lineages.

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Section: Resultsmentioning

confidence: 99%

Section: Acknowledgmentsmentioning

confidence: 97%

Human Papillomavirus Type 16 Genetic Variants: Phylogeny and Classification Based on E6 and LCR

Cornet

Gheit

Franceschi

et al. 2012

J Virol

145

152

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“…The HPV genome of two randomly selected samples of the E1-1374 ∧ 63nt E-G350 variant and two additional randomly selected samples of the E1-1374 ∧ 63nt E-C109/G350 variant were completely sequenced using primers and conditions from the study by Bhattacharjee et al [15] with additional modifications. Thus, several additional primer pairs were used for the sequencing of the E1 region: E1-A1 (5'-CTCAGAAACCATAATCTACC) with E1–B2 (5'-CTAATAGTAACACAACCATTCC), E1–A2 (5'-CAAAGTTTAGCATGTTCATGG) with E1–B4 (5'-GTAGCATCATCTAACATACC), E1–A3 (5'-CACAGGCAAAAATTGTAAAGG) with E1–B5 (5'-GTCTATATGGTCACGTAGG), and E1-A4 (5'-GTTAGATGATGCTACAGTGCC) with E1–B5 primer.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, several additional primer pairs were used for the sequencing of the E1 region: E1-A1 (5'-CTCAGAAACCATAATCTACC) with E1–B2 (5'-CTAATAGTAACACAACCATTCC), E1–A2 (5'-CAAAGTTTAGCATGTTCATGG) with E1–B4 (5'-GTAGCATCATCTAACATACC), E1–A3 (5'-CACAGGCAAAAATTGTAAAGG) with E1–B5 (5'-GTCTATATGGTCACGTAGG), and E1-A4 (5'-GTTAGATGATGCTACAGTGCC) with E1–B5 primer. Cycling parameters consisted of initial denaturation for 5 minutes at 95°C, 40 cycles of 30 seconds of denaturation at 95°C, 45 seconds of annealing at 55°C, 1 minute of elongation at 72°C with final elongation of 7 minutes at 72 ° C. The primers L1–2, from Bhattacharjee et al [15] were replaced with Alt16L1-F (5'-AGGTCGTGGTCAGCCATTAG) and Alt16L1-R (5'-GGGGATCTTCTTTAGGTGCTG). Cycling parameters were: initial denaturation for 2 minutes at 95°C, 35 cycles of 20 seconds of denaturation at 95°C, 20 seconds of annealing at 63°C, and 50 seconds elongation at 72°C with final elongation of 7 minutes at 72°C.…”

Section: Methodsmentioning

confidence: 99%

Characterization and Whole Genome Analysis of Human Papillomavirus Type 16 E1-1374∧63nt Variants

et al. 2012

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Background The variation of the most common Human papillomavirus (HPV) type found in cervical cancer, the HPV16, has been extensively investigated in almost all viral genes. The E1 gene variation, however, has been rarely studied. The main objective of the present investigation was to analyze the variability of the E6 and E1 genes, focusing on the recently identified E1-1374 ∧ 63nt variant. Methodology/Principal Findings Variation within the E6 of 786 HPV16 positive cervical samples was analyzed using high-resolution melting, while the E1-1374 ∧ 63nt duplication was assayed by PCR. Both techniques were supplemented with sequencing. The E1-1374 ∧ 63nt duplication was linked with the E-G350 and the E-C109/G350 variants. In comparison to the referent HPV16, the E1-1374 ∧ 63nt E-G350 variant was significantly associated with lower grade cervical lesions (p = 0.029), while the E1-1374 ∧ 63nt E-C109/G350 variant was equally distributed between high and low grade lesions. The E1-1374 ∧ 63nt variants were phylogenetically closest to E-G350 variant lineage (A2 sub-lineage based on full genome classification). The major differences between E1-1374 ∧ 63nt variants were within the LCR and the E6 region. On the other hand, changes within the E1 region were the major differences from the A2 sub-lineage, which has been historically but inconclusively associated with high grade cervical disease. Thus, the shared variations cannot explain the particular association of the E1-1374 ∧ 63nt variant with lower grade cervical lesions. Conclusions/Significance The E1 region has been thus far considered to be well conserved among all HPVs and therefore uninteresting for variability studies. However, this study shows that the variations within the E1 region could possibly affect cervical disease, since the E1-1374 ∧ 63nt E-G350 variant is significantly associated with lower grade cervical lesions, in comparison to the A1 and A2 sub-lineage variants. Furthermore, it appears that the silent variation 109T>C of the E-C109/G350 variant might have a significant role in the viral life cycle and warrants further study.

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“…Details regarding subjects, samples, DNA isolation, HPV screening and determination of HPV16 genome physical status, RNA isolation and c-DNA preparation are described earlier from our laboratory. 27,28,32,[61][62][63][64] …”

Section: Samples and Subjectsmentioning

confidence: 99%

Impact of viral and host DNA methylations on HPV16-related cervical cancer pathogenesis

et al. 2017

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Epigenetic alterations within human papillomavirus (HPV) and host cellular genomes are known to occur during cervical carcinogenesis. Our objective was to analyse the influence of (1) methylation within two immunostimulatory CpG motifs within HPV16 E6 and E7 genes around the viral late promoter and their correlation, if any, with expression deregulation of host receptor (TLR9) and DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) and (2) global DNA methylation levels within CpGs of the repetitive Alu sequences, on cervical cancer (CaCx) pathogenesis. Significantly higher proportions of CaCx samples portrayed methylation in immunostimulatory CpG motifs, compared to HPV16-positive non-malignant samples, with cases harbouring episomal HPV16 showing decreased methylation compared to those with viral integration. A significant linear trend of TLR9 upregulation was recorded in the order of HPV-negative controls < HPV16-positive non-malignant samples < HPV16-positive CaCx cases. TLR9 upregulation in cases with episomal HPV16 was again higher among those with non-methylated immunostimulatory CpG motifs. Comparison of cases with HPV-negative controls revealed that DNMT3A was significantly downregulated only among integrated cases, DNMT3B was significantly overexpressed among both categories of cases, although at variable levels, while DNMT1 failed to show any deregulated expression among the cases. Global host DNA hypomethylation, also showed a significant linear increasing trend through the progressive CaCx development stages mentioned above and was most prominently higher among cases with episomal HPV16 as opposed to viral integration. Thus, HPV16 and host methylations appear to influence CaCx pathogenesis, with differential molecular signatures among CaCx cases with episomal and integrated HPV16.

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Characterization of sequence variations within HPV16 isolates among Indian women: Prediction of causal role of rare non-synonymous variations within intact isolates in cervical cancer pathogenesis

Cited by 24 publications

References 43 publications

Human Papillomavirus Type 16 Genetic Variants: Phylogeny and Classification Based on E6 and LCR

Human Papillomavirus Type 16 Genetic Variants: Phylogeny and Classification Based on E6 and LCR

Characterization and Whole Genome Analysis of Human Papillomavirus Type 16 E1-1374∧63nt Variants

Impact of viral and host DNA methylations on HPV16-related cervical cancer pathogenesis

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