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

Ordoñez, Rosa M.; Espinosa, Ana; Sánchez-González, Dolores Javier; Armendáriz‐Borunda, Juan; Berumen, Jaime

doi:10.1099/vir.0.19317-0

Cited by 47 publications

(36 citation statements)

References 39 publications

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“…More recently, it was suggested that in European variants the early E6/E7 gene transcription is repressed by the E2 protein and is frequently up-regulated by the interruption of the E2 gene during viral integration. In contrast, in tumor samples harboring Asian-American variants this gene was observed to be frequently retained (55). The association of Asian-American variants with retention of E1/E2 genes suggests that E2 nucleotide sequence variability could be an alternative mechanism up-regulating the expression of viral oncogenes.…”

Section: Nucleotide Variability and Oncogenic Potentialmentioning

confidence: 65%

Epidemiological and functional implications of molecular variants of human papillomavirus

Sichero¹,

Villa²

2006

Braz J Med Biol Res

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Human papillomavirus genomes are classified into molecular variants when they present more than 98% of similarity to the prototype sequence within the L1 gene. Comparative nucleotide sequence analyses of these viruses have elucidated some features of their phylogenetic relationship. In addition, human papillomavirus intratype variability has also been used as an important tool in epidemiological studies of viral transmission, persistence and progression to clinically relevant cervical lesions. Until the present, little has been published concerning the functional significance of molecular variants. It has been shown that nucleotide variability within the long control region leads to differences in the binding affinity of some cellular transcriptional factors and to the enhancement of the expression of E6 and E7 oncogenes. Furthermore, in vivo and in vitro studies revealed differences in E6 and E7 biochemical and biological properties among molecular variants. Nevertheless, further correlation with additional functional information is needed to evaluate the significance of genome intratypic variability. These results are also important for the development of vaccines and to determine the extent to which immunization with L1 virus-like particles of one variant could induce antibodies that cross-neutralize other variants. Key words Papillomavirus heterogeneityThe first evidence for the existence of different human papillomavirus (HPV) types was obtained in the early 1970's when it was observed that mRNA purified from plantar warts hybridized with DNA purified from other plantar warts but not from warts at other sites, including anogenital ones. In the following years, the genetic heterogeneity of HPV was confirmed by restriction fragment length polymorphism analysis and this was followed by an extensive and clear definition of HPV types based on DNA sequencing of different genes and the long control region (LCR) (1).HPV types are defined as a viral genome with an L1 late gene sequence that is at least 10% dissimilar from that of any other type. To date more than 120 different HPV genotypes associated with infections in humans have been described. In addition, the Papillomavirus Nomenclature Committee has established that HPV genomes be classified into molecular variants when they present more than 98% of similarity to the prototype

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Section: Nucleotide Variability and Oncogenic Potentialmentioning

confidence: 65%

Epidemiological and functional implications of molecular variants of human papillomavirus

Sichero¹,

Villa²

2006

Braz J Med Biol Res

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“…In Asian-American variants the E2 gene is usually retained in tumor samples suggesting that variability in this gene could be a mechanism of upregulating the transcription of early oncogenes. 44 It has also been observed that replication efficiency is higher among Asian-American as compared to European variants of HPV-16. 45,46 The efficient E1/ E2 expression and elevated viral replication during persistent infection could confer to variants from the Asian-American branch the enhanced oncogenic potential reported in some epidemiological studies.…”

Section: Discussionmentioning

confidence: 94%

High grade cervical lesions are caused preferentially by non‐European variants of HPVs 16 and 18

Sichero

Ferreira²,

Trottier

et al. 2007

Intl Journal of Cancer

194

134

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The intratypic variability of HPVs 16 and 18 has been extensively studied and has been used as an important tool in epidemiological studies of viral transmission, persistence and progression to clinically relevant cervical lesions. Infections by non-European variants of HPVs 16 and 18 are associated with an increased risk for the development of high grade squamous intraepithelial lesions (HSIL). Our aim was to correlate the intratypic molecular variability of both HPV types and risk of persistent infection and lesion outcome in a cohort study conducted in Brazil. We characterized molecular variants of HPV types 16 and 18 by sequencing a fragment of the LCR, and of the E6 and L1 genes, for HPV-16 variants only. For both types, European variants composed the most prevalent and diverse group. Persistent infections with HPV-18 were associated with continuous detection of European variants. However, risk for simultaneous detection of HSIL and HPV DNA was higher in women harboring non-European variants of HPV-16. The same trend was observed with HSIL detected during follow-up. Our study confirms the association between non-European variants and risk of cervical neoplasia, and highlights the importance of their geographic distribution for cervical cancer risk assessment. ' 2007 Wiley-Liss, Inc.Key words: human papillomavirus; molecular variants; oncogenic potential; cohort study; cervical neoplasia More than 120 different human papillomavirus (HPV) genotypes associated with infections in humans have been described, of which approximately 40 infect the anogenital area. Nearly 20 of these are classified as high-risk HPV types (HR-HPV) due to their association with cancer. In particular, HPVs 16 and 18 are the most common high-risk types in cancer biopsies, worldwide. 1 Their oncogenic potential has been demonstrated both in vitro and in vivo. 2 Nevertheless, only a minority of women infected with HPVs 16 and 18 develop neoplastic lesions. 3,4 Intratypic molecular variants of HPVs are characterized by differences in nucleotide sequence from the prototypic L1 gene of less than 2%. 5 Recently, full genome analysis of HPV-16 isolates revealed that 4% of the sequence is variable. 6 Moreover, these authors described a 9.9% amino acid variability within the eight HPV genes of the different HPV-16 molecular variants studied. The nucleotide variability of HPVs 16 and 18 has been extensively studied, and several molecular variants have been described on the basis of their geographical distribution. 7-9 Studies conducted in multiethnic populations have shown the association between Asian-American or other non-European variants of HPVs 16 and 18 and increased risk of persistent infection and development of cervical lesion. 4,10-13 Specific variants of HPVs 16 and 18 seem to be associated also with certain histopathological features of cervical neoplastic lesions. 10,14,15 In one study, Asian-American variants of both HPVs 16 and 18 were associated with squamous cell carcinomas and adenocarcinomas, while European variants were assoc...

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“…Direct in vitro evidence regarding differences in biologic properties between HPV31 variants has not been available. However, the variable biologic properties of HPV16 and HPV18 variants were demonstrated by studies in vitro, [30][31][32][33] showing that the variants of these types differed in their abilities to induce p53 degradation, keratinocyte differentiation, transcription of E6/E7 oncogenes and tumor formation. It is likely that some nucleotide alterations may work individually or jointly to alter the variants' oncogenic potentials and be responsible for the observed risk differences.…”

Section: Discussionmentioning

confidence: 99%

Association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2–3

Schiffman

Koutsky

et al. 2012

Intl Journal of Cancer

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Although the lineages of human papillomavirus type 31 (HPV31) variants are recognized, their clinical relevance is unknown. The purpose of our study was to examine risk of cervical intraepithelial neoplasia Grades 2-3 (CIN2/3) by HPV31 variants. Study subjects were women who participated in the atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion Triage Study and who had HPV31 infections detected at one or more visits. They were followed semi-annually over 2 years for detection of HPV DNA and cervical lesion. HPV31 isolates were characterized by DNA sequencing and assigned into 1 of 3 variant lineages. CIN2/3 was histologically confirmed in 127 (27.0%) of the 470 HPV31-positive women, 83 diagnosed at the first HPV31-positive visit and 44 thereafter. The odds ratio for the association of 2-year cumulative risk of CIN2/3 was 1.7 (95% CI: 1.0-2.9) for infections with A variants and 2.2 (95% CI: 1.2-3.9) for infections with B variants as compared to those with C variants. Among women without CIN2/3 at the first HPV31-positive visit, the risk of subsequent CIN2/3 was 2.2-fold greater for those with A variants (95% CI: 1.0-4.8) and 2.0-fold greater for those with B variants (95% CI: 0.9-4.9) as compared to those with C variants. Similar associations were observed when CIN3 was used as the endpoint. The findings from our study help to tag HPV31 variants that differ in risk of CIN2/3 and to explain in part why some HPV31 infections regress spontaneously and others lead to disease progression.Cervical infection with human papillomavirus (HPV) types is a necessary cause of cervical cancer and its precursor, cervical intraepithelial neoplasia Grades 2-3 (CIN2/3). 1-3 To date, >150 papillomavirus types have been fully characterized and classified, from the higher to lower taxon, as genera, species and type. 4,5 HPV types are known to differ in their tropisms and oncogenic potentials. Studies of the intratypic variation, i.e., the variant, a level below the taxon of type, have focused mainly on HPV16 and HPV18, showing that some variants were more aggressive than others. [6][7][8][9][10][11][12] HPV31 is one of the oncogenic types, most closely related to HPV16. Prevalence of some HPV types may vary geographically. Results from a recent meta-analysis (including 215 studies worldwide) have shown that on average prevalence of HPV31 infection ranks fourth, after types 16, 18 and 45, in cases of cervical cancer and second, only after type 16, in women with high-grade squamous intraepithelial lesion (referring both to cytologically detected high-grade lesions and histologically diagnosed CIN2/3 or carcinoma in situ in this analysis). 1 Clinical relevance of HPV31 variants has been rarely described, 13-15 although the intratypic variations in the L1, E6, E7 and long control region were recognized. 14-21 A recent study by Chen et al. 22 has defined HPV31 variants as A, B and C lineages based on the whole genome analyses. This provides a basis to view the variant as a distinct phylogenet...

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

Cited by 47 publications

References 39 publications

Epidemiological and functional implications of molecular variants of human papillomavirus

Epidemiological and functional implications of molecular variants of human papillomavirus

High grade cervical lesions are caused preferentially by non‐European variants of HPVs 16 and 18

Association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2–3

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