The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China

Song, Zhilin; Cui, Yanru; Li, Qiufu; Deng, Junhang; Ding, Xianping; He, Jiaoyu; Liu, Yiran; Ju, Zhuang; Fang, Lizhen

doi:10.1186/s12985-021-01565-5

Cited by 7 publications

(8 citation statements)

References 53 publications

(72 reference statements)

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“…No positive selection sites for HPV16 E6 and E7 genes have been reported in central China [ 37 ]. No positive selection sites for HPV52 E6 and E7 genes have been reported in central and Southwest China [ 38 , 39 ]. In addition, selective pressure analysis from non-Asian population showed different results, with 10R, 14H, 83V in HPV E6 and 85G in HPV16 E7 under positive selective pressure [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic analysis and antigenic epitope prediction for E6 and E7 of Alpha-papillomavirus 9 in Taizhou, China

Yuan,

Yan,

Gan

et al. 2024

BMC Genomics

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Background Alpha-papillomavirus 9 (α-9) is a member of the human papillomavirus (HPV) α genus, causing 75% invasive cervical cancers worldwide. The purpose of this study was to provide data for effective treatment of HPV-induced cervical lesions in Taizhou by analysing the genetic variation and antigenic epitopes of α-9 HPV E6 and E7. Methods Cervical exfoliated cells were collected for HPV genotyping. Positive samples of the α-9 HPV single type were selected for E6 and E7 gene sequencing. The obtained nucleotide sequences were translated into amino acid sequences (protein primary structure) using MEGA X, and positive selection sites of the amino acid sequences were evaluated using PAML. The secondary and tertiary structures of the E6 and E7 proteins were predicted using PSIPred, SWISS-MODEL, and PyMol. Potential T/B-cell epitopes were predicted by Industrial Engineering Database (IEDB). Results From 2012 to 2023, α-9 HPV accounted for 75.0% (7815/10423) of high-risk HPV-positive samples in Taizhou, both alone and in combination with other types. Among these, single-type-positive samples of α-9 HPV were selected, and the entire E6 and E7 genes were sequenced, including 298 HPV16, 149 HPV31, 185 HPV33, 123 HPV35, 325 HPV52, and 199 HPV58 samples. Compared with reference sequences, 34, 12, 10, 2, 17, and 17 nonsynonymous nucleotide mutations were detected in HPV16, 31, 33, 35, 52, and 58, respectively. Among all nonsynonymous nucleotide mutations, 19 positive selection sites were selected, which may have evolutionary significance in rendering α-9 HPV adaptive to its environment. Immunoinformatics predicted 57 potential linear and 59 conformational B-cell epitopes, many of which are also predicted as CTL epitopes. Conclusion The present study provides almost comprehensive data on the genetic variations, phylogenetics, positive selection sites, and antigenic epitopes of α-9 HPV E6 and E7 in Taizhou, China, which will be helpful for local HPV therapeutic vaccine development.

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Section: Discussionmentioning

confidence: 99%

Phylogenetic analysis and antigenic epitope prediction for E6 and E7 of Alpha-papillomavirus 9 in Taizhou, China

Yuan,

Yan,

Gan

et al. 2024

BMC Genomics

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“…Thus, more studies are needed to prove its role in CC. It was interesting to us that the long control region ( LCR) of HPV16 and HPV52 was found to have a high permanent binding site for the SOX9 transcription factor ( Xi et al, 2017 ; Song et al, 2021 ; Mane et al, 2022 ), and these may be new targets for the treatment of HPV-associated CC.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of SOX9 in cervical cancer: Bioinformatics and experimental approaches

Chen

Zeng

et al. 2022

Front. Genet.

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Among gynecological cancers, cervical cancer is a common malignancy and remains the leading cause of cancer-related death for women. However, the exact molecular pathogenesis of cervical cancer is not known. Hence, understanding the molecular mechanisms underlying cervical cancer pathogenesis will aid in the development of effective treatment modalities. In this research, we attempted to discern candidate biomarkers for cervical cancer by using multiple bioinformatics approaches. First, we performed differential expression analysis based on cervical squamous cell carcinoma and endocervical adenocarcinoma data from The Cancer Genome Atlas database, then used differentially expressed genes for weighted gene co-expression network construction to find the most relevant gene module for cervical cancer. Next, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the module genes, followed by using protein–protein interaction network analysis and Cytoscape to find the key gene. Finally, we validated the key gene by using multiple online sites and experimental methods. Through weighted gene co-expression network analysis, we found the turquoise module was the highest correlated module with cervical cancer diagnosis. The biological process of the module genes focused on cell proliferation, cell adhesion, and protein binding processes, while the Kyoto Encyclopedia of Genes and Genomes pathway of the module significantly enriched pathways related to cancer and cell circle. Among the module genes, SOX9 was identified as the hub gene, and its expression was associated with cervical cancer prognosis. We found the expression of SOX9 correlates with cancer-associated fibroblast immune infiltration in immune cells by Timer2.0. Furthermore, cancer-associated fibroblast infiltration is linked to cervical cancer patients’ prognosis. Compared to those in normal adjacent, immunohistochemical and real-time quantitative polymerase chain reaction (qPCR) showed that the protein and mRNA expression of SOX9 in cervical cancer were higher. Therefore, the SOX9 gene acts as an oncogene in cervical cancer, interactive with immune infiltration of cancer-associated fibroblasts, thereby affecting the prognosis of patients with cervical cancer.

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“…Among all HPV types in China, the infection rate of HPV52 was relatively low in the late 1990s but has gradually increased since then [ 6 , 7 , 22 ]. Recently, HPV52 has become the most prevalent type among the Chinese population [ 6 , 8 , 9 , 17 – 19 , 30 ]. Furthermore, the oncogenicity of HPV is mainly attributable to the combined effects of the E6 and E7 oncoproteins.…”

Section: Discussionmentioning

confidence: 99%

“…The primer sequences specific for the E6 and E7 genes of HPV52 were 52E6E7_F 5′-ACCCACAACCACTTTTTTTTAT-3’ and 52E6E7_R 5′-TTGCCTCTACTTCAAACCAGCC-3’, which were cited from a recently published article [ 8 ]. Primers were synthesized by BGI company (Hangzhou, China).…”

Section: Methodsmentioning

confidence: 99%

“…In our previous Taizhou area HPV studies, the results suggested that Chinese women have the highest susceptibility to the HPV52 type, but the carcinogenic ability of HPV52 was relatively weaker than that of HPV16 or HPV58 [ 5 – 7 ]. The genomic characterization of HPV52 has obvious epidemiological characteristics, especially the (sub)lineages and single nucleotide substitutions in the two major oncogenes E6 and E7 , which may increase the risk of infection with HPV52 in Chinese women [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Genetic variability in the E6 and E7 oncogenes of HPV52 and its prevalence in the Taizhou area, China

Yang

Zhang

et al. 2022

Virol J

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Background Human papillomavirus (HPV) 52 is one of the prevalent oncogenic HPV genotypes in East Asia. Chinese women have the highest susceptibility to the HPV52 type, but research data on HPV52 genetic variability and its carcinogenicity in China is lacking. Methods The present study aimed to investigate the genetic variability of HPV52 currently circulating among Chinese women by PCR sequencing the entire E6 and E7 oncogenes. HPV52 sequence alignment, genetic heterogeneity analyses and maximum-likelihood phylogenetic tree construction were performed by BioEdit software and MEGA X software. Results Between 2016 and 2018, the overall HPV infection rate was 21.3%, of which HPV52 was the most prevalent high-risk type (17.2%) in the Taizhou area, China. A total of 339 single HPV52-positive samples were included in this study. We obtained 27 distinct variation patterns of HPV52 with the accession GenBank numbers ON529577-ON529603. Phylogenetic analysis showed that 96.6% of HPV52 variants belonged to lineage B, which seemed to be uniquely defined by G350T, A379G (K93R) in the E6 gene and C751T, A801G in the E7 gene. Due to the dominance of lineage B in our study population, the results could not be used to assess the association of the HPV52 (sub)lineage with the risk of cervical lesions. In addition, no significant trends were observed between the nucleotide substitutions of HPV52 variants and the risk of cervical carcinogenesis. Conclusion Our data showed that HPV52 variants were strongly biased towards lineage B. These results confirmed that cervical lesions in the Taizhou area are highly attributable to HPV52, which may be due to the high infection rate of lineage B in the population.

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The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China

Cited by 7 publications

References 53 publications

Phylogenetic analysis and antigenic epitope prediction for E6 and E7 of Alpha-papillomavirus 9 in Taizhou, China

Phylogenetic analysis and antigenic epitope prediction for E6 and E7 of Alpha-papillomavirus 9 in Taizhou, China

Prognostic value of SOX9 in cervical cancer: Bioinformatics and experimental approaches

Genetic variability in the E6 and E7 oncogenes of HPV52 and its prevalence in the Taizhou area, China

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