scholarly journals Genetic Variability and Phylogeny of Human Papillomavirus Type 16 Based On E6, E7 and L1 Genes in Central China

2021 ◽  
Author(s):  
Shuizhong Han ◽  
Xiaochuan Wang ◽  
Xiaojing Wang ◽  
Shuaijun Wang ◽  
Li Ma
Keyword(s):  
B Cell ◽  
Phylogenetic Trees ◽  
Central China ◽  
Reference Sequence ◽  
B Cell Epitopes ◽  
Hpv16 E6 ◽  
Synonymous Mutations ◽  
Secondary Structure Analysis ◽  
E6 And E7 ◽  
E7 Proteins

Abstract In the current study, a total of 74 single-infected HPV16 samples from females attending the gynecological outpatient clinic in four cities of Henan province were collected and applied to the L1, E6 and E7 sequencing. Variations of the HPV16 L1, E6 and E7 genes were characterized by comparison with reference sequence and the secondary structure analysis were conducted. Phylogenetic trees based on the L1 and E6-E7 sequences were constructed separately. B-cell epitopes of the HPV16 E6 and E7 proteins were predicted further. A total of thirty-seven novel variations, including twenty L1 genes and seventeen E6-E7 genes were identified. Compared with the reference sequence, twenty-eight variations (1.8%, 28/1596) were identified in L1 gene sequences and 10/28 (35.7%) were non-synonymous mutations. For E6-E7 sequences, twenty-five novel gene changes (including 16 mutations (3.4%, 16/477) in E6 gene, 9 mutations (3.0%, 9/297) in E7 gene) were found, 18/25 (72.0%) were non-synonymous and 10/28 (35.7%) were non-synonymous mutations. Phylogenetic analysis showed that 56.8% (42/74) of the samples were A1 sublineages, 37.8% (28/74) were A4, 4.1% (3/74) were A3 and 1.4% (1/74) was A2 sublineages. On the prediction of B-cell epitopes, seven potent epitopes for E6 and four for E7 were identified. Amino mutations, including L90V, R62K, R142Q and F76L in E6, S63F and N29S/H in E7 changed the score. HPV16 variants prevalent in the central China belong to European A1 sublineages. Sequences of HPV16 L1, E6 and E7 in this study may provide assistant for the improvement of HPV vaccines.

The HPV16 E6 and E7 proteins and the radiation resistance of cervical carcinoma

2001 ◽  
Vol 15 (8) ◽  
pp. 1445-1447 ◽  
Author(s):  
Lynne Hampson ◽  
El Said Abd El Hady ◽  
James V. Moore ◽  
Henry Kitchener ◽  
Ian N. Hampson
Keyword(s):  
Cervical Carcinoma ◽  
Radiation Resistance ◽  
Hpv16 E6 ◽  
E6 And E7 ◽  
E7 Proteins

scholarly journals Prediction and Evolution of B Cell Epitopes of Surface Protein in SARS-CoV-2

2020 ◽  
Author(s):  
Jerome R Lon ◽  
Yunmeng Bai ◽  
Bingxu Zhong ◽  
Fuqaing Cai ◽  
Hongli Du
Keyword(s):  
B Cell ◽  
Vaccine Development ◽  
Surface Protein ◽  
The Other ◽  
Reference Sequence ◽  
Prediction Methods ◽  
Whole Genome ◽  
B Cell Epitopes ◽  
Conformational Epitopes ◽  
Linear Epitopes

AbstractThe discovery of epitopes is helpful to the development of SARS-CoV-2 vaccine. The sequences of the surface protein of SARS-CoV-2 and its proximal sequences were obtained by BLAST, the sequences of the whole genome of SARS-CoV-2 were obtained from the GenBank. Based on the NCBI Reference Sequence: NC_045512.2, the conformational and linear B cell epitopes of the surface protein were predicted separately by various prediction methods. Furthermore, the conservation of the epitopes, the adaptability and other evolutionary characteristics were also analyzed. 7 epitopes were predicted, including 5 linear epitopes and 2 conformational epitopes, one of the linear and one of the conformational were coincide. The epitope D mutated easily, but the other epitopes were very conservative and the epitope C was the most conservative. It is worth mentioning that all of the 6 dominated epitopes were absolutely conservative in nearly 1000 SARS-CoV-2 genomes, and they deserved further study. The findings would facilitate the vaccine development, had the potential to be directly applied on the treatment in this disease, but also have the potential to prevent the possible threats caused by other types of coronavirus.

scholarly journals Prediction and Evolution of B Cell Epitopes of Surface Protein in SARS-CoV-2

2020 ◽  
Author(s):  
Jerome Rumdon Lon ◽  
Yunmeng Bai ◽  
Bingxu Zhong ◽  
Fuqiang Cai ◽  
Hongli Du
Keyword(s):  
B Cell ◽  
Vaccine Development ◽  
Surface Protein ◽  
Conformational Epitope ◽  
Reference Sequence ◽  
Effective Vaccine ◽  
Antigenic Determinants ◽  
B Cell Epitopes ◽  
Linear Epitopes ◽  
Long Acting

Abstract Background In order to obtain antibodies that recognize natural proteins, it is possible to predict the antigenic determinants of natural proteins, which are eventually embodied as polypeptides. The polypeptides can be coupled with corresponding vectors to stimulate the immune system to produce corresponding antibodies, which is also a simple and effective vaccine development method. The discovery of epitopes is helpful to the development of SARS-CoV-2 vaccine. Methods The analyses were related to epitopes on 3 proteins, including spike(S), envelope(E) and membrane(M) proteins, which were associated with the lipid envelope of the SARS-CoV-2. Based on the NCBI Reference Sequence: NC_045512.2, the conformational and linear B cell epitopes of the surface protein were predicted separately by various prediction methods. Furthermore, the conservation of the epitopes, the adaptability and other evolutionary characteristics were also analyzed, the sequences of the whole genome of SARS-CoV-2 were obtained from the GISAID. Results 7 epitopes were predicted, including 6 linear epitopes and 1 conformational epitope. One of the linear and one of the conformational consist of identical sequence, but represent different forms of epitopes. It is worth mentioning that all of the 6 dominated epitopes were conservative in nearly 3500 SARS-CoV-2 genomes, and they showed a phenomenon which is helpful to obtain stable and long-acting epitopes under the condition of high frequency of amino acid mutation, and deserved further study at the experiment level. Conclusion The findings would facilitate the vaccine development, had the potential to be directly applied on the prevention in this disease, but also have the potential to prevent the possible threats caused by other types of coronavirus.

scholarly journals SARS-CoV-2 and ORF3a: Non-Synonymous Mutations and Polyproline Regions

2020 ◽  
Author(s):  
Elio Issa ◽  
Georgi Merhi ◽  
Balig Panossian ◽  
Tamara Salloum ◽  
Sima Tokajian
Keyword(s):  
Amino Acids ◽  
Immune Response ◽  
B Cell ◽  
Immune Evasion ◽  
Protein Sequences ◽  
B Cell Epitopes ◽  
Synonymous Mutations ◽  
Viral Spread ◽  
Rapid Accumulation ◽  
The Impact

AbstractThe effect of the rapid accumulation of non-synonymous mutations on the pathogenesis of SARS-CoV-2 is not yet known. To predict the impact of non-synonymous mutations and polyproline regions identified in ORF3a on the formation of B-cell epitopes and their role in evading the immune response, nucleotide and protein sequences of 537 available SARS-CoV-2 genomes were analyzed for the presence of non-synonymous mutations and polyproline regions. Mutations were correlated with changes in epitope formation. A total of 19 different non-synonymous amino acids substitutions were detected in ORF3a among 537 SARS-CoV-2 strains. G251V was the most common and identified in 9.9% (n=53) of the strains and was predicted to lead to the loss of a B-cell like epitope in ORF3a. Polyproline regions were detected in two strains (EPI_ISL_410486, France and EPI_ISL_407079, Finland) and affected epitopes formation. The accumulation of non-synonymous mutations and detected polyproline regions in ORF3a of SARS-CoV-2 could be driving the evasion of the host immune response thus favoring viral spread. Rapid mutations accumulating in ORF3a should be closely monitored throughout the COVID-19 pandemic.ImportanceAt the surge of the COVID-19 pandemic and after three months of the identification of SARS-CoV-2 as the disease-causing pathogen, nucleic acid changes due to host-pathogen interactions are insightful into the evolution of this virus. In this paper, we have identified a set of non-synonymous mutations in ORF3a and predicted their impact on B-cell like epitope formation. The accumulation of non-synonymous mutations in ORF3a could be driving protein changes that mediate immune evasion and favoring viral spread.

scholarly journals Human papillomavirus type 68 prevalence and genetic variability based on E6/E7 genes in Sichuan

2021 ◽  
Author(s):  
Jiaoyu He ◽  
Qiufu Li ◽  
Yuning Chen ◽  
Jianying Peng ◽  
Shiyu Ma ◽  
...  
Keyword(s):  
Positive Selection ◽  
B Cell ◽  
Malignant Tumors ◽  
Three Dimensional ◽  
Alpha Helix ◽  
Likelihood Method ◽  
Dimensional Structure ◽  
Therapeutic Vaccines ◽  
B Cell Epitopes ◽  
Synonymous Mutations

Abstract Background:Cervical cancer is one of the malignant tumors threatening women's health worldwide, only second to breast cancer. 99.7% cervical cancer was found to be associated with high-risk HPV (HR-HPV) persistent infections. HPV68 is a common HR-HPV, closely related to cervical cancer.Methods:Cell samples were collected by cervical scraped for HPV detecting and typing, and HPV 68 positive samples were selected out. Important E6, E7 genes of HPV 68 were sequenced and analyzed for the study of HPV 68 genetic polymorphisms. Phylogenetic tree of E6-E7 was constructed by Maximum likelihood method of MEGA v7.0 software. The selection pressure sites of HPV68 E6, E7 were predicted by codeml in the PAML 4.8. The secondary structure and three-dimensional structure of HPV68 E6, E7 were analyzed by PSIPRED server and SWISS-MODEL respectively. T-cell and B-cell antigen epitopes of HPV68 E6, E7 were predicted by immune epitope Database Analysis (IEDB) resource and ABCpred server respectivelyResults:a total of 10650 cell samples were collected for detecting and typing, and 2939 (27.60%, 2939/10650) positive samples were detected, 174 (5.92%, 174/2939) were HPV68; 150 HPV68 E6-E7 were successful amplified and analyzed, 32 nucleotide mutations were observed in this study, 50% (16/32) were non-synonymous mutations; among them, 4 non-synonymous mutations were detected in E6 gene (one in the Coil and three in the Strand), 12 were in E7 gene (four in the alpha helix, two in the Coil and six in the Strand). Phylogenetic analysis of HPV68 E6-E7 suggested that C was the most frequent HPV68 lineage in Sichuan China. 82-90SESVYATTL, 85-93VYATTLETI, 13-21KLPDLCRTL and 67-81-SCIKFYAKIRELRYY, 68-82CIKFYAKIRELRYYS, 66-80QSCIKFYAKIRELRY were the most potential HPV68 E6 HLA-Ⅰ, HLA-Ⅱepitopes respectively; and B-cell epitopes were 138-153CRHCWTSKREDRRRTR, 82-97SESVYATTLETITNTK. 92-101LLFMDSLNFV, 45-53AVNHHQHQL and 20-35EIEPVDLVCHEQLGDS were the most potential HPV68 E7 HLA-Ⅰand B-cell epitopes. 3 HPV68 E6 positive selection sites and 5 HPV68 E7 were detected, and they all had a certain influence on the proteins structure and epitopes affinity.Conclusion:Non-synonymous mutations of HPV 68 located in positive selection sites resulted in differences in protein structure and epitopes affinity, that may affect the pathogenicity and adaptability of HPV68 to the environment. HPV68 data enrichment is of great significance for understanding the inherent geographical and biological differences of HPV68 in china; and targeting potential epitopes for therapeutic vaccines may improve the effective of vaccines design for specific populations.

scholarly journals HPV16-E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by down regulating the expression of KIF7

2020 ◽  
Author(s):  
Yue Hu ◽  
Ming-Zhe Wu ◽  
Na-Jin Gu ◽  
Xue-Shan Qiu ◽  
En-Hua Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Genetic Manipulation ◽  
Lung Cancer Cells ◽  
Hpv16 E6 ◽  
E6 And E7 ◽  
E7 Proteins ◽  
First Time ◽  
New Evidence

Abstract Background: The E6 and E7 proteins in HPV16 are the main oncogenes in the occurrence of lung cancer. In recent studies, we had found that E6 and E7 downregulated the expression of LKB1 in lung cancer cells. However, it is not clear how E6 and E7 regulate LKB1 in lung cancer cells. Methods: The double directional genetic manipulation and Nuclear plasma separation technology were performed to explore the molecular mechanism of E6 and E7 inhibiting the antitumor activity of LKB1 in well-established lung cancer cell lines. Results: E6 but not E7 significantly downregulated the expression of tumor suppressor KIF7 at protein level, and the inhibition of KIF7 further reduced the expression of LKB1 both in the nuclei and in the cytoplasm, whereas reduced the expression of p-LKB1 in the cytoplasm only. Therefore, we suggested that HPV16 E6 but not E7 downregulates the antitumor activity of LKB1 by down regulating the expression of p-LKB1 in the cytoplasm only. Conclusion: We demonstrated for the first time that E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by downregulating the expression of KIF7. Our findings provided new evidence to support the important role of KIF7 in the pathogenesis of lung cancer and suggested new therapeutic targets.

scholarly journals HPV16-E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by down regulating the expression of KIF7

2020 ◽  
Author(s):  
Yue Hu ◽  
Ming-Zhe Wu ◽  
Na-Jin Gu ◽  
Xue-Shan Qiu ◽  
En-Hua Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Genetic Manipulation ◽  
Lung Cancer Cells ◽  
Hpv16 E6 ◽  
E6 And E7 ◽  
E7 Proteins ◽  
First Time ◽  
New Evidence

Abstract Background: The E6 and E7 proteins in HPV16 are the main oncogenes in the occurrence of lung cancer. In recent studies, we had found that E6 and E7 downregulated the expression of LKB1 in lung cancer cells. However, it is not clear how E6 and E7 regulate LKB1 in lung cancer cells. Methods: The double directional genetic manipulation and Nuclear plasma separation technology were performed to explore the molecular mechanism of E6 and E7 inhibiting the antitumor activity of LKB1 in well-established lung cancer cell lines. Results: E6 but not E7 significantly downregulated the expression of tumor suppressor KIF7 at protein level, and the inhibition of KIF7 further reduced the expression of LKB1 both in the nuclei and in the cytoplasm, whereas reduced the expression of p-LKB1 in the cytoplasm only. Therefore, we suggested that HPV16 E6 but not E7 downregulates the antitumor activity of LKB1 by down regulating the expression of p-LKB1 in the cytoplasm only. Conclusion: We demonstrated for the first time that E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by down regulating the expression of KIF7. Our findings provided new evidence to support the important role of KIF7 in the pathogenesis of lung cancer and suggested new therapeutic targets.

scholarly journals Prediction and Evolution of B Cell Epitopes of Surface Protein in SARS-CoV-2

2020 ◽  
Author(s):  
Jerome Rumdon Lon ◽  
Yunmeng Bai ◽  
Bingxu Zhong ◽  
Fuqaing Cai ◽  
Hongli Du
Keyword(s):  
B Cell ◽  
Vaccine Development ◽  
Surface Protein ◽  
The Other ◽  
Reference Sequence ◽  
Prediction Methods ◽  
Whole Genome ◽  
B Cell Epitopes ◽  
Conformational Epitopes ◽  
Linear Epitopes

Abstract Background The discovery of epitopes is helpful to the development of SARS-CoV-2 vaccine.Methods The sequences of the surface protein of SARS-CoV-2 and its proximal sequences were obtained by BLAST, the sequences of the whole genome of SARS-CoV-2 were obtained from the GenBank. Based on the NCBI Reference Sequence: NC_045512.2, the conformational and linear B cell epitopes of the surface protein were predicted separately by various prediction methods. Furthermore, the conservation of the epitopes, the adaptability and other evolutionary characteristics were also analyzed.Results 7 epitopes were predicted, including 5 linear epitopes and 2 conformational epitopes, one of the linear and one of the conformational were coincide. The epitope D mutated easily, but the other epitopes were very conservative and the epitope C was the most conservative. It is worth mentioning that all of the 6 dominated epitopes were absolutely conservative in nearly 1000 SARS-CoV-2 genomes, and they deserved further study.Conclusion The findings would facilitate the vaccine development, had the potential to be directly applied on the treatment in this disease, but also have the potential to prevent the possible threats caused by other types of coronavirus.

scholarly journals HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway via relieving miR-451 inhibitory effect on CAB39 in lung cancer cells

2020 ◽  
Vol 11 ◽  
pp. 204062232095714
Author(s):  
Hong-Miao Wang ◽  
Ying-Jie Lu ◽  
Ling He ◽  
Na-Jin Gu ◽  
Shi-Yu Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Flow Cytometry ◽  
Plasma Membrane ◽  
Glucose Uptake ◽  
Cancer Cells ◽  
Akt Pathway ◽  
Mrna Levels ◽  
Hpv16 E6 ◽  
E6 And E7 ◽  
E7 Proteins

Background: HPV16 E6/E7 proteins are the main oncogenes and only long-term persistent infection causes lung cancer. Our previous studies have shown that HPV16 E6/E7 protein up-regulates the expression of GLUT1 in lung cancer cells. However, whether E6 and E7 protein can promote the glucose uptake of GLUT1 and its molecular mechanism are unclear. Methods: The regulatory relationships of E6 or E7, miR-451, CAB39, PI3K/AKT, and GLUT1 were detected by double directional genetic manipulations in lung cancer cell lines. Immunofluorescence and flow cytometry were used to detect the effect of CAB39 on promoting the translocation to the plasma membrane of GLUT1. Flow cytometry and confocal microscopy were performed to detect the glucose uptake levels of GLUT1. Results: The overexpression both E6 and E7 proteins significantly down-regulated the expression level of miR-451, and the loss of miR-451 further up-regulated the expression of its target gene CAB39 at both protein and mRNA levels. Subsequently, CAB39 up-regulated the expression of GLUT1 at both protein and mRNA levels. Our results demonstrated that HPV16 E6/E7 up-regulated the expression and activation of GLUT1 through the HPV–miR-451–CAB39–GLUT1 axis. More interestingly, we found that CAB39 prompted GLUT1 translocation to the plasma membrane and glucose uptake, and this promotion depended on the PI3K/AKT pathway. Conclusion: Our findings provide new evidence to support the critical roles of miR-451 and CAB39 in the pathogenesis of HPV-related lung cancer.

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