Identification of a novel human papillomavirus type 16 E1 gene variant with potentially reduced oncogenicity

Sabol, Ivan; Matovina, Mihaela; Gašperov, Nina Milutin; Grce, Magdalena

doi:10.1002/jmv.21304

Cited by 14 publications

(25 citation statements)

References 32 publications

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“…For example, there is a relatively common SNP with the E6 ORF (T350G), which is a non-synonymous change resulting in an amino acid variation (L83V). This variation/mutation might be related to higher oncogenic potential [23], [24], [76], [77], or not [33], [78], [79]; in the current study it was not found to be associated with increased risk. It has been suggested that this mutation is associated with CC in a heterogenic form by world region [58].…”

Section: Discussioncontrasting

confidence: 50%

Human Papillomavirus 16 Non-European Variants Are Preferentially Associated with High-Grade Cervical Lesions

et al. 2014

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HPV16 accounts for 50–70% of cervical cancer cases worldwide. Characterization of HPV16 variants previously indicated that they differ in risks for viral persistence, progression to cervical precancer and malignant cancer. The aim of this study was to examine the association of severity of disease with HPV16 variants identified in specimens (n = 281) obtained from a Cervical Pathology and Colposcopy outpatient clinic in the University Hospital of Espírito Santo State, Southeastern Brazil, from April 2010 to November 2011. All cytologic and histologic diagnoses were determined prior to definitive treatment. The DNA was isolated using QIAamp DNA Mini Kit and HPV was detected by amplification with PGMY09/11 primers and positive samples were genotyped by RFLP analyses and reverse line blot. The genomes of the HPV16 positive samples were sequenced, from which variant lineages were determined. Chi2 statistics was performed to test the association of HPV16 variants between case and control groups. The prevalence of HR-HPV types in

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Section: Discussioncontrasting

confidence: 50%

Human Papillomavirus 16 Non-European Variants Are Preferentially Associated with High-Grade Cervical Lesions

et al. 2014

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“…Previously we found a 63-nucleotide duplication, at position 1374 within the E1 gene (E1-1374 ∧ 63nt), in about 10% of HPV16 positive cervical samples. This finding indicates that this particular variation is relatively common in the Croatian population [7], and possibly elsewhere. The same variant was also confirmed to be present in neighbouring Slovenia, in about 8% of samples [8].…”

Section: Introductionmentioning

confidence: 62%

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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“…E1 was found to be more conserved than other regions [21], and the substitutions of G1515A, A1842G (9/21), A2269T (8/21), and G2337A (5/21) were frequently found in E1. E5 variations have been considered unrelated to malignant transformation.…”

Section: Resultsmentioning

confidence: 99%

Physical Status and Variant Analysis of Human Papillomavirus 16 in Women from Shanghai

Guo

Zhu

et al. 2015

Gynecol Obstet Invest

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Background/Aims: Human papillomavirus type 16 (HPV16) is the cause of more than half of all cases of cervical cancer. Genetic mutations in HPV16 and the integration of HPV16 DNA in the human genome are considered important genetic changes in cervical lesion progression. However, limited data concerning HPV16 lineages and physical integration status have been reported for Shanghai, China. The current study analyzed the genetic mutations in complete HPV16 genomes and the physical integration status of HPV16 DNA. Methods: A total of 30 samples of cervical exfoliated cells from patients with HPV16 infection were collected. The entire HPV16 genome was isolated, amplified by PCR and directly sequenced. The physical integration status was determined by 3′RACE nested PCR. Results: A total of 13 integration sites were identified, including 9 in common fragile sites and 1 not close to any fragile sites. Phylogenetic analysis identified two HPV lineages: the European (E) lineage and the East Asian (EA) lineage. Amino acid changes of D25E and N29S were the most common variations across the genome. The HPV16 early genes E1 and E7 and the late gene L1 tended to be highly conserved, whereas the early genes E2, E4 and E6 were more variable. Furthermore, 10 novel variations were identified in this study, which led to the 3 amino acid changes of S23I in E2 and E244K and T269I in E2/E4. Conclusion: Integrated HPV16 viruses were detected in all stages of cervical samples. Many variants in E2, E4, E7, and the long control region co-varied with E6 variations and helped to define the HPV16 lineages.

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Identification of a novel human papillomavirus type 16 E1 gene variant with potentially reduced oncogenicity

Cited by 14 publications

References 32 publications

Human Papillomavirus 16 Non-European Variants Are Preferentially Associated with High-Grade Cervical Lesions

Human Papillomavirus 16 Non-European Variants Are Preferentially Associated with High-Grade Cervical Lesions

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

Physical Status and Variant Analysis of Human Papillomavirus 16 in Women from Shanghai

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