Mutational landscape and intra-host diversity of human papillomavirus type 16 long control region and E6 variants in cervical samples

Escobar-Escamilla, Noé; González-Martínez, Blanca Estela; Araiza-Rodríguez, Adnan; Fragoso-Fonseca, David Esaú; Pedroza-Torres, Abraham; Landa-Flores, Magaly Guadalupe; Garcés-Ayala, Fabiola; Mendieta-Condado, Edgar; Díaz-Quiñonez, José Alberto; Castro-Escarpulli, Graciela; Ramírez–González, José Ernesto

doi:10.1007/s00705-019-04407-6

Cited by 13 publications

(11 citation statements)

References 43 publications

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“…Forty SNPs in the LCR were detected in our studied samples, and C7434G, G7519A and G7190T were the most commonly detected. A very high percentage of G7519A and G7190T detection was also shown in other studies conducted in England, Poland and Mexico [20,40,41]. Both mutations are located within YY1 transcriptional factor binding sites that have been reported to be involved in the regulation of HPV16 E6/E7 oncogenic transcripts [42].…”

Section: Discussionsupporting

confidence: 65%

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Analysis of Human Papillomavirus (HPV) 16 Variants Associated with Cervical Infection in Italian Women

Martinelli

Clara

Sotgiu

et al. 2020

IJERPH

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This study aims to evaluate HPV16 variants distribution in a population of Italian women living in two different regions (Lombardy and Sardinia) by sequence analyses of HPV16-positive cervical samples, in order to reconstruct the phylogenetic relationship among variants to identify the currently circulating lineages. Analyses were conducted starting from DNA isolated from 67 HPV16-positive cervical samples collected from two different Italian centres (31 from Lombardy and 36 from Sardinia) of women with normal and abnormal cervical cytology. The entire long control region (LCR) and 300 nt of the E6 gene was sequenced to identify intra-type variants. Sequence comparison and phylogenetic analysis were made using a distance-based neighbour joining method (NJ) and Kimura two-parameter model. Data obtained reported that Italian sequences mainly belonged to the European lineage, in particular sublineage A2. Only five sequences clustered in non-European branches: two in North American lineage (sublineage D1), two in African-1 (sublineage B1) and one in African-2. A new 27 nucleotide duplication in the central segment of the LCR region was found in a sequence obtained from a sample isolated in Sardinia. A predominance of European variants was detected, with some degree of variability among the studied HPV16 strains. This study contributes to the implementation of data regarding the molecular epidemiology of HPV16 variants.

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Section: Discussionsupporting

confidence: 65%

“…The median interquartile range (IQR) age of the study population was 36 (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)…”

Section: Study Populationmentioning

confidence: 99%

Analysis of Human Papillomavirus (HPV) 16 Variants Associated with Cervical Infection in Italian Women

Martinelli

Clara

Sotgiu

et al. 2020

IJERPH

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“…For HPV-16, the T350G (83L>V) mutation we detected is the most common mutation on the E6 gene of HPV-16 [30-32]. Several studies have shown that the T350G mutant may cause persistent virus infection and further increase cancer risk [31-34]. It is reported that T350G variants can down-regulate the expression of E-cadherin, which is an adhesion protein that acts cell-cell adhesion.…”

Section: Discussionmentioning

confidence: 99%

AutoVEM2: a flexible automated tool to analyze candidate key mutations and epidemic trends for virus

Jiang

et al. 2021

Preprint

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In our previous work, we developed an automated tool, AutoVEM, for real-time monitoring the candidate key mutations and epidemic trends of SARS-CoV-2. In this research, we further developed AutoVEM into AutoVEM2. AutoVEM2 is composed of three modules, including call module, analysis module, and plot module, which can be used modularly or as a whole for any virus, as long as the corresponding reference genome is provided. Therefore, it is much more flexible than AutoVEM. Here, we analyzed three existing viruses by AutoVEM2, including SARS-CoV-2, HBV and HPV-16, to show the functions, effectiveness and flexibility of AutoVEM2. We found that the N501Y locus was almost completely linked to the other 16 loci in SARS-CoV-2 genomes from the UK and Europe. Among the 17 loci, 5 loci were on the S protein and all of the five mutations cause amino acid changes, which may influence the epidemic traits of SARS-CoV-2. And some candidate key mutations of HBV and HPV-16, including T350G of HPV-16 and C659T of HBV, were detected. In brief, we developed a flexible automated tool to analyze candidate key mutations and epidemic trends for any virus, which would become a standard process for virus analysis based on genome sequences in the future.

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“…Although the HPV16 LCR sequence alterations G7518A and G7191T influence the binding site of fundamental host transcriptional factors, no association of the respective mutations with the development of cervical lesions has been found (Ref. 143).…”

Section: Long Control Regionmentioning

confidence: 99%

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

Bletsa¹,

Zagouri

Amoutzias

et al. 2021

Expert Rev. Mol. Med.

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Human papillomavirus 16 (HPV16) infection is the aetiologic factor for the development of cervical dysplasia and is regarded as highly carcinogen, because it is implicated in more than 50% of cervical cancer cases, worldwide. The tumourigenic potential of HPV16 has triggered the extensive sequence analysis of viral genome in order to identify nucleotide variations and amino acid substitutions that influence viral oncogenicity and subsequently the initiation and progression of cervical cancer. Nowadays, specific mutations of HPV16 DNA have been associated with an increased risk of high-grade squamous intraepithelial lesions and invasive cervical cancer (ICC) development, including E6 : Q14H, H78Y, L83V, Ε7 : N29S, S63F, E2 : H35Q, P219S, T310K, E5 : I65V, whereas highly conserved regions of viral DNA have been extensively characterised. In addition, numerous novel HPV16 mutations are observed among the studied populations from various geographic regions, hence advocating that different HPV16 strains seem to emerge with different tumourigenic capacities. The present review focuses on the variability of the early genes and the long control region, emphasising on the association of specific mutations with the development of severe dysplasia. Finally, it evaluates whether specific regions of HPV16 DNA are able to serve as valuable biomarkers for cervical cancer risk.

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Mutational landscape and intra-host diversity of human papillomavirus type 16 long control region and E6 variants in cervical samples

Cited by 13 publications

References 43 publications

Analysis of Human Papillomavirus (HPV) 16 Variants Associated with Cervical Infection in Italian Women

Analysis of Human Papillomavirus (HPV) 16 Variants Associated with Cervical Infection in Italian Women

AutoVEM2: a flexible automated tool to analyze candidate key mutations and epidemic trends for virus

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

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