scholarly journals Human Papillomavirus 16 Variants May Be Identified by E6 Gene Analysis

Intervirology ◽  
2015 ◽  
Vol 58 (3) ◽  
pp. 143-148 ◽  
Author(s):  
Nerea Fontecha ◽  
Miren Basaras ◽  
Elixabete Arrese ◽  
Silvia Hernáez ◽  
Daniel Andía ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Sequence Analysis ◽  
Genetic Variability ◽  
Asian American ◽  
Gene Analysis ◽  
Multiple Infection ◽  
Hpv 16 ◽  
E6 Gene ◽  
European Variant ◽  
The Relationship

Aims: The aims of the study were (1) to characterize the genetic variability of human papillomavirus (HPV) genotype 16 in the E6 region when this genotype is present in multiple infection samples, (2) to assess the prevalence of variants in our region and (3) to analyze the relationship between variants, patients' ages and pathology. Methods: The Clinical Microbiology and Infection Control Department analyzed samples which were positive for genotype 16 and other genotypes from 2007 to 2013. Variants were assigned to European, Euro-German, Asian, Asian-American or African lineage by sequence analysis. The relationship among variants, age and different types of lesion was studied. Results: In HPV-16 sequence analysis, the European variant was detected in 85.10% of samples, the Asian-American in 7.80%, the African in 4.25% and the Euro-German in 2.83% of specimens. Sequence genetic variability showed 16 nucleotide substitutions. Moreover, non-European variants were mainly found in old women and in isolates from high-grade squamous intraepithelial lesions since European variants were mainly detected in negative cytologies. Conclusion: Multiple infections may take effect on nucleotide substitution and the appearance of recombinant samples. Single gene analysis makes it impossible to detect recombination which has a great influence on drug response and vaccine strategies. Thus, E6 gene analysis would be enough to identify HPV-16 intratypic variants but not to confirm the results.

An oligoarray for the detection of human papillomavirus type 16 variants

2007 ◽  
Vol 17 (5) ◽  
pp. 1083-1091 ◽  
Author(s):  
P. Mendoza-Lorenzo ◽  
R. Maldonado ◽  
R. Pacheco ◽  
A. MÉNDEZ ◽  
P. Piña-Sánchez ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Asian American ◽  
Dna Sequences ◽  
Gene Mutations ◽  
Hpv 16 ◽  
Reliable Technique ◽  
Short Oligonucleotide ◽  
Hpv E6 ◽  
E6 Gene ◽  
Specialized Equipment

On the basis of human papillomavirus (HPV) E6 gene mutations, there are more than five variants of HPV 16. We applied a sensitive and specific stacking hybridization assay using an oligoarray for the detection of Asian–American (AA) and European (E) (E350G) HPV 16 variants. A simple glass slide was coated with capture probes consisting of short oligonucleotide DNA sequences (7–9 mers) specific for AA and E variants. Two different regions of the E6 HPV 16 gene were amplified with a set of two primers, which were used as target DNA. These targets were preannealed with auxiliary labeled oligonucleotides and hybridized to the oligoarray in the presence of specific and complementary capture probes. Our designed array based on shorter capture probes successfully discriminated between HPV 16 AA and E variants. The present DNA oligoarray system could be useful as a reliable technique for HPV 16 detection and does not require specialized equipment; nevertheless, further intra- and interlaboratory studies are needed.

scholarly journals Transcriptional Activation of the Telomerase hTERT Gene by Human Papillomavirus Type 16 E6 Oncoprotein

2001 ◽  
Vol 75 (9) ◽  
pp. 4467-4472 ◽  
Author(s):  
Tim Veldman ◽  
Izumi Horikawa ◽  
J. Carl Barrett ◽  
Richard Schlegel
Keyword(s):  
Human Papillomavirus ◽  
Transcriptional Activation ◽  
Transcriptional Control ◽  
Regulatory Region ◽  
Rnase Protection ◽  
Hpv 16 ◽  
Htert Gene ◽  
Human Papillomavirus Type 16 ◽  
E6 Gene

ABSTRACT The E6 and E7 oncogenes of human papillomavirus type 16 (HPV-16) are sufficient for the immortalization of human genital keratinocytes in vitro. The products of these viral genes associate with p53 and pRb tumor suppressor proteins, respectively, and interfere with their normal growth-regulatory functions. The HPV-16 E6 protein has also been shown to increase the telomerase enzyme activity in primary epithelial cells by an unknown mechanism. We report here that a study using reverse transcription-PCR and RNase protection assays in transduced primary human foreskin keratinocytes (HFKs) shows that the E6 gene (but not the E7 gene) increases telomerase hTERT gene transcription coordinately with E6-induced telomerase activity. In these same cells, the E6 gene induces a 6.5-fold increase in the activity of a 1,165-bp 5′ promoter/regulatory region of the hTERT gene, and this induction is attributable to a minimal 251-bp sequence (−211 to +40). Furthermore, there is a 35-bp region (+5 to +40) within this minimal E6-responsive promoter that is responsible for 60% of E6 activity. Although the minimal hTERT promoter contains Myc-responsive E-box elements and recent studies have suggested a role for Myc protein in hTERT transcriptional control, we found no alterations in the abundance of either c-Myc or c-Mad in E6-transduced HFKs, suggesting that there are other or additional transcription factors critical for regulating hTERT expression.

scholarly journals Human Papillomavirus Type Distribution and Correlation with Cyto-Histological Patterns in Women from the South of Italy

2009 ◽  
Vol 2009 ◽  
pp. 1-4 ◽  
Author(s):  
Paola Menegazzi ◽  
Luisa Barzon ◽  
Giorgio Palù ◽  
Elisa Reho ◽  
Luigi Tagliaferro
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Hpv Infection ◽  
Multiple Infection ◽  
Multiple Infections ◽  
The South ◽  
Hpv 16 ◽  
Specific Distribution ◽  
Hpv Types ◽  
High Risk Hpv

Human papillomavirus (HPV) type-specific distribution was evaluated in genital samples collected from 654 women from the South of Italy undergoing voluntary screening and correlated with cyto-histological abnormalities. HPV DNA was detected in 45.9% of the samples, 41.7% of which had multiple infection and 89.0% had high-risk HPV infection. The prevalence of HPV infection and the rate of multiple infections decreased with age, suggesting natural selection of HPV types with better fitness. In line with other Italian studies, the most common HPV types were HPV-6 and HPV-16, followed by HPV-51, HPV-31, HPV-53, and HPV-66, in women with both normal and abnormal cytology. Cervical intraepithelial lesions grade 2 or 3 were associated with high-risk HPV-16, HPV-18, HPV-31, and HPV-51 infection. These data indicate that prophylactic HPV vaccination is expected to reduce the burden of HPV-related cervical lesions in this population, but also suggest the potential utility of new vaccines with larger type coverage.

Variant Lineages of Human Papillomavirus Type 18 in Northeast China Populations Characterized by Sequence Analysis of E6, E7, and L1 Regions

2012 ◽  
Vol 22 (6) ◽  
pp. 930-936 ◽  
Author(s):  
Zhengrong Sun ◽  
Jianhua Liu ◽  
Guili Wang ◽  
Weiqiang Zhou ◽  
Chao Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Amino Acid ◽  
Sequence Analysis ◽  
Asian American ◽  
Northeast China ◽  
Amino Acid Substitutions ◽  
The Novel ◽  
Novel Variants ◽  
Hpv 18

IntroductionIn cervical cancer, human papillomavirus (HPV) 18 is predominantly related to adenocarcinomas. Variant lineages of HPV type 16 have been well characterized, whereas the knowledge about HPV 18 variants is limited in Northeast China.MethodsTo identify prevalent and novel HPV 18 variants in Northeast China, theE6,E7, andL1genes of HPV 18 from patients with cervical lesion were amplified and sequenced, and intratypic variants were analyzed by comparing to the known phylogenetic branches.ResultsThe HPV-18 E6 variants of our studied strains belong to 2 main branches: Asian-American (AA) variants in 81.5% and European (E) variants in 18.5%. Strains with variations of C287G, T482C, and C519A inE6and C751T inE7were novel variants. All theL1genes of the analyzed HPV 18 strains had 4 C-G transversions at nucleotide positions of 5701, 6460, 6625, and 6842 and one G-A transition at position 5503. Moreover, strains with L1 nucleotide variations of A5920T, A6431T, and G6987A leading to amino acid substitutions of A164V, Q334P/H, and D520N are novel variants.ConclusionsBased on theE6gene, the prevalent HPV 18 in Northeast China was AA and E variants. Besides some common variations reported before, some new variations in theE6,E7, andL1genes were found. Data about the novel variations found in theL1gene of HPV 18 variants may be helpful to design the diagnostic reagents and vaccine for naturally infected HPV 18 in Northeast China.

Prediction of Human Papillomavirus 16 E6 Gene Expression and Cervical Intraepithelial Neoplasia Progression by Methylation Status

2009 ◽  
Vol 19 (3) ◽  
pp. 321-325 ◽  
Author(s):  
Pavla Hublarova ◽  
Roman Hrstka ◽  
Pavla Rotterova ◽  
Leopold Rotter ◽  
Marie Coupkova ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Methylation Status ◽  
Gene Promoter ◽  
Intraepithelial Neoplasia ◽  
Hpv 16 ◽  
Human Papillomavirus 16 ◽  
E6 Gene ◽  
Asymptomatic Women

Introduction:Human papillomavirus (HPV) infection represents the most important risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. We aimed to analyze the consequences of methylation of the E6 gene promoter in distinct stages of HPV-16-induced cellular transformation to assess its importance for disease progression.Methods:Human papillomavirus 16 was detected by sensitive polymerase chain reaction (PCR). Determination of E6 gene promoter methylation was analyzed by digestion with specific restriction endonuclease McrBC followed by PCR amplification. Expression of the E6 gene was determined by quantitative real-time PCR.Results:Of 103 cervical smears from asymptomatic women with no cytological and colposcopic abnormalities, 20.4% were HPV-16-positive. Human papillomavirus 16 was present in 44.4% of 18 patients with CIN I, in 62.2% of 143 patients with CIN II/III, and in 74.2% of 31 cervix carcinoma specimens. The incidence of HPV-16 in all lesions compared with asymptomatic women was statistically significant (P< 0.001, Pearsonχ2test). Methylation was detected in 81% (n = 21) of HPV-16-positive asymptomatic smears compared with 62.5% in CIN I (n = 8), 31.5% (n = 89) in CIN II/III, and 43.4% (n = 23) in carcinomas; a statistical significance between lesions and healthy women was found (P< 0.001, Pearsonχ2test). Expression of E6 mRNA correlated with methylation status (P= 0.010, Mann-WhitneyUtest).Conclusions:We conclude that methylation of the E6 gene promoter in HPV-16 genome is a predictive biomarker for cervical cancer progression by regulating the expression of the E6 oncogene.

scholarly journals Complete Genome Sequences of Eight Human Papillomavirus Type 16 Asian American and European Variant Isolates from Cervical Biopsies and Lesions in Indian Women: TABLE 1 

2016 ◽  
Vol 4 (3) ◽  
Author(s):  
Paramita Mandal ◽  
Bornali Bhattacharjee ◽  
Shrinka Sen ◽  
Amrapali Bhattacharya ◽  
Rahul Roy Chowdhury ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Asian American ◽  
Complete Genome ◽  
Etiological Agent ◽  
Genome Sequences ◽  
Indian Women ◽  
Human Papillomavirus Type 16 ◽  
European Variant

Human papillomavirus type 16 (HPV16), a member of thePapillomaviridaefamily, is the primary etiological agent of cervical cancer. Here, we report the complete genome sequences of four HPV16 Asian American variants and four European variants, isolated from cervical biopsies and scrapings in India.

Genetic variability in the major capsid L1 protein of human papillomavirus type 16 (HPV-16) and 18 (HPV-18)

2011 ◽  
Vol 11 (8) ◽  
pp. 2119-2124 ◽  
Author(s):  
E. Frati ◽  
S. Bianchi ◽  
D. Colzani ◽  
A. Zappa ◽  
G. Orlando ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Genetic Variability ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein ◽  
Hpv 18

scholarly journals Enhanced oncogenicity of Asian-American human papillomavirus 16 is associated with impaired E2 repression of E6/E7 oncogene transcription

2004 ◽  
Vol 85 (6) ◽  
pp. 1433-1444 ◽  
Author(s):  
Rosa M. Ordóñez ◽  
Ana María Espinosa ◽  
Dolores Javier Sánchez-González ◽  
Juan Armendáriz-Borunda ◽  
Jaime Berumen
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Asian American ◽  
Long Control Region ◽  
Hpv 16 ◽  
E2 Protein ◽  
Human Papillomavirus 16 ◽  
E2 Gene ◽  
E7 Oncogene

Asian-American (AA) variants of human papillomavirus 16 (HPV-16) are linked to a high incidence of cervical cancer in Mexico, with some evidence strongly suggesting that they are more oncogenic than European (E) variants, including their association with younger women and their higher associated risk of cervical cancer. Differences in the regulation of viral E6/E7 oncogene transcription by the E2 protein may be involved in the higher oncogenicity of AA variants. In E variants, E6/E7 oncogene transcription is repressed by the E2 protein and is frequently up-regulated by the destruction of the E2 gene during viral integration. In contrast, the E2 gene is retained in full in most AA-positive carcinomas, raising the possibility of alternative mechanisms for increasing viral oncogene transcription. The authors investigated whether the higher oncogenicity of AA variants is linked to differences in E6/E7 oncogene transcription and the mechanism of E2 deactivation. E6/E7 and E1/E2 transcripts were explored by RT-PCR in 53 HPV-16-positive cervical carcinomas, 39 retaining (20 European and 19 AA) and 14 having lost (12 European and 2 AA) the E1/E2 genes, and transcription repression activity of the AA E2 genes was tested in four cell lines that constitutively express the β-galactosidase reporter or E6/E7 genes driven by the viral long control region. E6/E7 oncogene transcripts were found in all carcinomas, but only those positive for AA variants with E1/E2 genes had complete E2 transcripts. E2 transcripts were down-regulated by splicing in E-positive carcinomas retaining E1/E2. AA E2 genes were impaired for repression of E6/E7 oncogene transcription in vivo. These results suggest that E6/E7 oncogene expression starts earlier in AA than E variant infections, since E variants need E2 to be destroyed or down-regulated.

scholarly journals Upstream Regulatory Region Alterations Found in Human Papillomavirus Type 16 (HPV-16) Isolates from Cervical Carcinomas Increase Transcription, ori Function, and HPV Immortalization Capacity in Culture

2009 ◽  
Vol 83 (15) ◽  
pp. 7457-7466 ◽  
Author(s):  
Michael J. Lace ◽  
Christina Isacson ◽  
James R. Anson ◽  
Attila T. Lörincz ◽  
Sharon P. Wilczynski ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Nucleotide Sequence ◽  
Asian American ◽  
Viral Genome ◽  
Regulatory Protein ◽  
Regulatory Region ◽  
Early Gene ◽  
Regulatory Sequences ◽  
Upstream Regulatory Region ◽  
Hpv 16

ABSTRACT Human papillomavirus (HPV) DNAs isolated from cervical and head and neck carcinomas frequently contain nucleotide sequence alterations in the viral upstream regulatory region (URR). Our study has addressed the role such sequence changes may play in the efficiency of establishing HPV persistence and altered keratinocyte growth. Genomic mapping of integrated HPV type 16 (HPV-16) genomes from 32 cervical cancers revealed that the viral E6 and E7 oncogenes, as well as the L1 region/URR, were intact in all of them. The URR sequences from integrated and unintegrated viral DNA were found to harbor distinct sets of nucleotide substitutions. A subset of the altered URRs increased the potential of HPV-16 to establish persistent, cell growth-altering viral-genome replication in the cell. This aggressive phenotype in culture was not solely due to increased viral early gene transcription, but also to augmented initial amplification of the viral genome. As revealed in a novel ori-dependent HPV-16 plasmid amplification assay, the altered motifs that led to increased viral transcription from the intact genome also greatly augmented HPV-16 ori function. The nucleotide sequence changes correlate with those previously described in the distinct geographical North American type 1 and Asian-American variants that are associated with more aggressive disease in epidemiologic studies and encompass, but are not limited to, alterations in previously characterized sites for the negative regulatory protein YY1. Our results thus provide evidence that nucleotide alterations in HPV regulatory sequences could serve as potential prognostic markers of HPV-associated carcinogenesis.

scholarly journals Influence of human papillomavirus type 16 (HPV-16) E2 polymorphism on quantification of HPV-16 episomal and integrated DNA in cervicovaginal lavages from women with cervical intraepithelial neoplasia

2008 ◽  
Vol 89 (7) ◽  
pp. 1716-1728 ◽  
Author(s):  
Naoufel Azizi ◽  
Jessica Brazete ◽  
Catherine Hankins ◽  
Deborah Money ◽  
Julie Fontaine ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Viral Load ◽  
Cervical Intraepithelial Neoplasia ◽  
Asian American ◽  
Intraepithelial Neoplasia ◽  
Hpv 16 ◽  
Viral Loads ◽  
Human Papillomavirus Type 16 ◽  
Immunodeficiency Virus ◽  
Intraepithelial Lesion

Integrated human papillomavirus type 16 (HPV-16) viral loads are currently estimated by quantification with real-time PCR of HPV-16 E6 (RT-E6 and HPV-16 PG) and E2 (RT-E2-1) DNA. We assessed the influence of HPV-16 E2 polymorphism on quantification of integrated HPV-16 DNA in anogenital specimens. HPV-16 E2 was sequenced from 135 isolates (123 from European and 12 from non-European lineages). An assay targeting conserved HPV-16 E2 sequences (RT-E2-2) was optimized and applied with RT-E6 and RT-E2-1 on 139 HPV-16-positive cervicovaginal lavages collected from 74 women [58 human immunodeficiency virus (HIV)-seropositive and 16 HIV-seronegative]. Ratios of HPV-16 copies measured with RT-E2-2 and RT-E2-1 obtained with African 2 (median=3.23, range=1.92–3.49) or Asian–American (median=3.78, range=1.47–37) isolates were greater than those obtained with European isolates (median=1.02, range=0.64–1.80; P<0.02 for each comparison). The distribution of HPV-16 E2 copies measured in 139 samples with RT-E2-2 (median=6150) and RT-E2-1 (median=8960) were different (P<0.0001). The risk of high-grade cervical intraepithelial neoplasia (CIN-2,3) compared with women without CIN was increased with higher HPV-16 total [odds ratio (OR)=2.17, 95 % confidence interval (CI)=1.11–4.23], episomal (OR=2.14, 95 % CI=1.09–4.19), but not for HPV-16 integrated viral load (OR=1.71, 95 % CI=0.90–3.26), after controlling for age, race, CD4 count, HIV and HPV-16 polymorphism. The proportion of samples with an E6/E2 ratio >2 in women without squamous intraepithelial lesion (7 of 35) was similar to that of women with CIN-2,3 (5 of 11, P=0.24) or CIN-1 (5 of 14, P=0.50). HPV-16 E2 polymorphism was a significant factor that influenced measures of HPV-16 integrated viral load.

Sign in / Sign up

Export Citation Format

Share Document