Intratype HPV16 sequence variation within LCR of isolates from asymptomatic carriers and cervical cancers

Schmidt, Marcin; Kędzia, Witold; Goździcka-Józefiak, Anna

doi:10.1016/s1386-6532(01)00189-5

Cited by 26 publications

(20 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mutation most frequently observed in LCR was G7521A in the binding site of the transcription factor YY1 (Pande et al, 2008). In this study, in accordance to other authors (Yamada et al, 1997;Schmidt et al, 2001;Kammer et al, 2002;Pande et al, 2008;Shang et al, 2011), the mutation most frequently detected in the LCR region was G7521A, found in the African lineages and most European ones. Thus, only 20% of analyzed samples presented homology with the prototype sequence.…”

Section: 1151 Mutation Detection Of E6 and Lcr Genes From Hpv 16 Asssupporting

confidence: 91%

“…The analysis of the nucleotide changes found in cervical cancer isolates showed that the changes were mainly located within or close to YY1 binding sites, while in asymptomatic carriers these changes presented as a wide variety of transcription factor binding sites (Schmidt et al, 2001). The mutation most frequently observed in LCR was G7521A in the binding site of the transcription factor YY1 (Pande et al, 2008).…”

Section: 1151 Mutation Detection Of E6 and Lcr Genes From Hpv 16 Assmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Section: 1151 Mutation Detection Of E6 and Lcr Genes From Hpv 16 Asssupporting

confidence: 91%

Section: 1151 Mutation Detection Of E6 and Lcr Genes From Hpv 16 Assmentioning

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

View full text Add to dashboard Cite

show abstract

“…Multiple functional YY1 sites have been identified in HPV regulatory sequences (this study), in HPV-18 (Bauknecht et al, 1992) and in extrachromosomal (May et al, 1994) and integrated (Schmidt et al, 2001) HPV-16 DNA isolates from clinical cervical carcinoma biopsies. Mutations or deletions of multiple HPV/YY1 sites in defined intratypic HPV-16 variants relieve downregulation of P97 promoter activity and plasmid replication (Hubert, 2005) and contribute to a greater potential for the altered HPV genome to transform primary keratinocytes in culture (Lace et al, 2009).…”

Section: Yy1 Downregulation Of Hpv Transcriptionmentioning

confidence: 80%

“…It has also been shown that extrachromosomal or integrated HPV-16 DNA isolated from malignant cervical biopsies contains mutated or deleted YY1 sites upstream of the P97 start site (May et al, 1994;Schmidt et al, 2001), resulting in increased P97 transcription, origin of replication (ori) function, initial plasmid amplification and virus immortalization capacity (Lace et al, 2009). It has also been suggested that YY1 bound to several upstream motifs targets transcriptional activators such as AP-1 (O'Connor et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Cellular factor YY1 downregulates the human papillomavirus 16 E6/E7 promoter, P97, in vivo and in vitro from a negative element overlapping the transcription-initiation site

Lace

Yamakawa

Ushikai

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

Cellular factors that bind to cis sequences in the human papillomavirus 16 (HPV-16) upstream regulatory region (URR) positively and negatively regulate the viral E6 and E7 oncogene promoter, P97. DNase I footprinting has revealed the binding of cellular proteins to two previously undetected cis elements overlapping and 3′ of the transcription-initiation site of the P97 promoter. Mutations within homologous motifs found in both of these cis elements abolished their negative function in vivo and the binding of the same cellular complex in vitro. This factor was identified as YY1 by complex mobility and binding specificity in comparison with vaccinia virus-expressed, purified recombinant YY1 protein and by antigenic reactivity with YY1 antisera. Cis mutations in the ‘initiator’ YY1 site activated the P97 promoter in vivo and in vitro. P97 was also activated threefold in vitro by depletion of endogenous YY1 with wild-type, but not mutant, YY1 oligonucleotides from the IgH kappa E3′ enhancer. Furthermore, increasing concentrations of exogenous, purified recombinant YY1 repressed wild-type P97 transcript levels by up to threefold, but did not influence the P97 promoter mutated in the ‘initiator’ YY1 site. Thus, the promoter-proximal YY1 site was not necessary for correct transcription initiation at the P97 promoter, but was found to be required for downregulation of P97 transcription in vivo and in vitro. In contrast to other viral and cellular promoters, where YY1 is thought to function as a positive transcription-‘initiator’ factor, HPV-16 P97 transcription is downregulated by YY1 from a critical motif overlapping the transcription start site.

show abstract

“…Some of the additional single-nucleotide substitutions within the URR sequences also potentially affect previously defined binding sites for YY1; these included the most frequently detected alteration, at nt 7520, which was shown to disrupt YY1 binding (53). Four such sequence alterations potentially affecting known YY1 motifs were introduced into the HPV-16 wt promoter construct to determine if they were sufficient to account for the observed increase in P97 promoter activities.…”

Section: Resultsmentioning

confidence: 99%

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

Lace

Isacson

Anson

et al. 2009

J Virol

View full text Add to dashboard Cite

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.

show abstract

Intratype HPV16 sequence variation within LCR of isolates from asymptomatic carriers and cervical cancers

Cited by 26 publications

References 55 publications

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

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

Cellular factor YY1 downregulates the human papillomavirus 16 E6/E7 promoter, P97, in vivo and in vitro from a negative element overlapping the transcription-initiation site

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

Contact Info

Product

Resources

About