Molecular and evolutionary analysis of HPV16 E6 and E7 genes in Greek women

2013 ◽  
Vol 62 (11) ◽  
pp. 1688-1696 ◽  
Author(s):  
D. Tsakogiannis ◽  
A. Papadopoulou ◽  
G. Kontostathi ◽  
I. G. A. Ruether ◽  
Z. Kyriakopoulou ◽  
...  
Keyword(s):  
Viral Evolution ◽  
Greek Population ◽  
Low Grade ◽  
Evolutionary Analysis ◽  
Amino Acid Residues ◽  
Hpv16 E6 ◽  
E6 Gene ◽  
E6 And E7 ◽  
Cervical Cancer Development ◽  
The Individual

Human papillomavirus type 16 (HPV16) non-European variants have been associated with persistent infection and cervical cancer development, while the L83V variant of the E6 gene has been correlated with the progression of cervical malignancy. The present study investigated the presence of the HPV16 L83V variant in Greek women. Molecular evolutionary analysis of the HPV16 E6 and E7 oncogenes was conducted in order to estimate the evolution of the HPV16 genome in the Greek population. The E6 L83V variant was found in 78.2 % of high- and 64.28 % of low-grade specimens. Moreover, the prototype and E6 L83V variants were both prevalent in high- and low-grade malignancies in Greek women. Selective pressure analysis of the individual amino acid residues of HPV16 sequences from the Greek population indicates that codon 83 of the E6 protein, as well as codon 85 of the E7 protein, are undergoing positive selection. Novel sequence variations were recorded within the E6 and E7 genes in cervical samples, characterized as (T350G) European variants. However, no signal of intratypic recombination event was identified within the E6–E7 region. Molecular and evolutionary analyses of HPV16 genomes from distinct geographical locations might provide valuable information about viral evolution and oncogenecity.

scholarly journals The Human Papillomavirus Type 16 E6 Gene Alone Is Sufficient To Induce Carcinomas in Transgenic Animals

1999 ◽  
Vol 73 (7) ◽  
pp. 5887-5893 ◽  
Author(s):  
Shiyu Song ◽  
Henry C. Pitot ◽  
Paul F. Lambert
Keyword(s):  
Animal Experiments ◽  
Basal Layer ◽  
Transgenic Animals ◽  
Human Papillomaviruses ◽  
Skin Tumors ◽  
Benign Tumors ◽  
Hpv16 E6 ◽  
Adult Mice ◽  
E6 Gene ◽  
E6 And E7

ABSTRACT High-risk human papillomaviruses (HPVs) are the causative agents of certain human cancers. HPV type 16 (HPV16) is the papillomavirus most frequently associated with cervical cancer in women. The E6 and E7 genes of HPV are expressed in cells derived from these cancers and can transform cells in tissue culture. Animal experiments have demonstrated that E6 and E7 together cause tumors. We showed previously that E6 and E7 together or E7 alone could induce skin tumors in mice when these genes were expressed in the basal epithelia of the skin. In this study, we investigated the role that the E6 gene plays in carcinogenesis. We generated K14E6 transgenic mice, in which the HPV16 E6 gene was directed in its expression by the human keratin 14 promoter (hK14) to the basal layer of the epidermis. We found that E6 induced cellular hyperproliferation and epidermal hyperplasia and caused skin tumors in adult mice. Interestingly, the tumors derived from E6 were mostly malignant, as opposed to the tumors from E7 mice, which were mostly benign. This result leads us to hypothesize that E6 may contribute differently than E7 to HPV-associated carcinogenesis; whereas E7 primarily contributes to the early stages of carcinogenesis that lead to the formation of benign tumors, E6 primarily contributes to the late stages of carcinogenesis that lead to malignancy.

scholarly journals Intrabodies targeting human papillomavirus 16 E6 and E7 oncoproteins for therapy of established HPV-associated tumors

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Francesca Paolini ◽  
Carla Amici ◽  
Mariantonia Carosi ◽  
Claudia Bonomo ◽  
Paola Di Bonito ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Cellular Transformation ◽  
Neoplastic Progression ◽  
Single Chain ◽  
Hpv16 E6 ◽  
Associated Lesions ◽  
E6 And E7

Abstract Background The oncogenic activity of the high risk human papillomavirus type 16 (HPV16) is fully dependent on the E6 and E7 viral oncoproteins produced during viral infection. The oncoproteins interfere with cellular homeostasis by promoting proliferation, inhibiting apoptosis and blocking epithelial differentiation, driving the infected cells towards neoplastic progression. The causal relationship between expression of E6/E7 and cellular transformation allows inhibiting the oncogenic process by hindering the activity of the two oncoproteins. We previously developed and characterized some antibodies in single-chain format (scFvs) against the HPV16 E6 and E7 proteins, and demonstrated both in vitro and in vivo their antitumor activity consisting of protective efficacy against tumor progression of HPV16-positive cells. Methods Envisioning clinical application of the best characterized anti-HPV16 E6 and –HPV16 E7 scFvs, we verified their activity in the therapeutic setting, on already implanted tumors. Recombinant plasmids expressing the anti-HPV16 E6 scFvI7 with nuclear targeting sequence, or the anti-HPV16 E7 scFv43M2 with endoplasmic reticulum targeting sequence were delivered by injection followed by electroporation to three different preclinical models using C57/BL6 mice, and their effect on tumor growth was investigated. In the first model, the HPV16+ TC-1 Luc cells were used to implant tumors in mice, and tumor growth was measured by luciferase activity; in the second model, a fourfold number of TC-1 cells was used to obtain more aggressively growing tumors; in the third model, the HPV16+ C3 cells where used to rise tumors in mice. To highlight the scFv possible mechanism of action, H&E and caspase-3 staining of tumor section were performed. Results We showed that both the anti-HPV16 E6 and HPV16 E7 scFvs tested were efficacious in delaying tumor progression in the three experimental models and that their antitumor activity seems to rely on driving tumor cells towards the apoptotic pathway. Conclusion Based on our study, two scFvs have been identified that could represent a safe and effective treatment for the therapy of HPV16-associated lesions. The mechanism underlying the scFv effectiveness appears to be leading cells towards death by apoptosis. Furthermore, the validity of electroporation, a methodology allowed for human treatment, to deliver scFvs to tumors was confirmed.

scholarly journals Association of cervical carcinogenesis risk with HPV16 E6 and E7 variants in the Taizhou area, China

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mei-Zhen Dai ◽  
Yi Qiu ◽  
Xing-Hong Di ◽  
Wei-Wu Shi ◽  
Hui-Hui Xu
Keyword(s):  
Cervical Cancer ◽  
Cervical Carcinogenesis ◽  
Chi Square ◽  
Major Health Problem ◽  
Hpv16 E6 ◽  
Exact Test ◽  
Chi Square Test ◽  
E6 And E7

Abstract Background Human papillomavirus (HPV) type 16 accounts for a larger share of cervical cancer and has been a major health problem worldwide for decades. The progression of initial infection to cervical cancer has been linked to viral sequence properties; however, the role of HPV16 variants in the risk of cervical carcinogenesis, especially with longitudinal follow-up, is not fully understood in China. Methods We aimed to investigate the genetic variability of HPV16 E6 and E7 oncogenes in isolates from cervical exfoliated cells. Between December 2012 and December 2014, a total of 310 single HPV16-positive samples were selected from women living in the Taizhou area, China. Sequences of all E6 and E7 oncogenes were analysed by PCR-sequencing assay. Detailed sequence comparison, genetic heterogeneity analyses and maximum-likelihood phylogenetic tree construction were performed with BioEdit Sequence Alignment Editor and MEGA X software. Data for cytology tests and histological diagnoses were obtained from our Taizhou Area Study with longitudinal follow-up for at least 5 years. The relationship between HPV16 variants and cervical carcinogenesis risk was analysed by the chi-square test or Fisher’s exact test. Results In this study, we obtained 64 distinct variation patterns with the accession GenBank numbers MT681266-MT681329. Phylogenetic analysis revealed that 98.3% of HPV16 variants belong to lineage A, in which the A4 (Asian) sublineage was dominant (64.8%), followed by A2 (12.1%), A1 (11.4%), and A3 (10.0%). The A4 (Asian) sublineage had a higher risk of CIN2+ than the A1–3 (European) sublineages (OR = 2.69, 95% CI = 1.04–6.97, P < 0.05). Furthermore, nucleotide variation in HPV16 E6 T178G is associated with the development of cervical cancer. Conclusion These data could provide novel insights into the role of HPV16 variants in cervical carcinogenesis risk in China.

scholarly journals Phylogenetic analysis and predicted functional effect of protein mutations of E6 and E7 HPV16 strains isolated in Indonesia

2015 ◽  
Vol 24 (4) ◽  
pp. 197-205
Author(s):  
Dwi Wulandari ◽  
Lisnawati Rachmadi ◽  
Tjahjani M. Sudiro
Keyword(s):  
Amino Acids ◽  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Asian American ◽  
Protein Function ◽  
Single Amino Acid ◽  
Hpv16 E6 ◽  
E6 And E7 ◽  
Neutral Mutations

Background: E6 and E7 are oncoproteins of HPV16. Natural amino acid variation in HPV16 E6 can alter its carcinogenic potential. The aim of this study was to analyze phylogenetically E6 and E7 genes and proteins of HPV16 from Indonesia and predict the effects of single amino acid substitution on protein function. This analysis could be used to reduce time, effort, and research cost as initial screening in selection of protein or isolates to be tested in vitro or in vivo.Methods: In this study, E6 and E7 gene sequences were obtained from 12 samples of  Indonesian isolates, which  were compared with HPV16R (prototype) and 6 standard isolates in the category of European (E), Asian (As), Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and North American (NA) branch from Genbank. Bioedit v.7.0.0 was used to analyze the composition and substitution of single amino acids. Phylogenetic analysis of E6 and E7 genes and proteins was performed using Clustal X (1.81) and NJPLOT softwares. Effects of single amino acid substitutions on protein function of E6 and E7 were analysed by SNAP.Results: Java variants and isolate ui66* belonged to European branch, while the others belonged to Asian and African branches. Twelve changes of amino acids were found in E6 and one in E7 proteins. SNAP analysis showed two non neutral mutations, i.e. R10I and C63G in E6 proteins. R10I mutations were found in Af-2 genotype (AF472509) and Indonesian isolates (Af2*), while C63G mutation was found only in Af2*.Conclusion: E6 proteins of HPV16 variants were more variable than E7. SNAP analysis showed that only E6 protein of African-2 branch had functional differences compared to HPV16R.

Regulation of Metabolism: A Cross Talk Between Gut Microbiota and Its Human Host

Physiology ◽  
2012 ◽  
Vol 27 (5) ◽  
pp. 300-307 ◽  
Author(s):  
Rémy Burcelin
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Low Grade ◽  
Gene Products ◽  
Individual Level ◽  
Obesity And Diabetes ◽  
Regulation Of Metabolism ◽  
Molecular Origin ◽  
The Individual ◽  
Low Grade Inflammation

The recent epidemic of obesity and diabetes and the diversity at the individual level could be explained by the intestinal microbiota-to-host relationship. More than four million gene products from the microbiome could interact with the immune system to induce a tissue metabolic infection, which is the molecular origin of the low-grade inflammation that characterizes the onset of obesity and diabetes.

High Grade Mental Deficiency in Relation to Differential Fertility

1947 ◽  
Vol 93 (391) ◽  
pp. 289-302 ◽  
Author(s):  
J. A. Fraser Roberts
Keyword(s):  
Genetic Factors ◽  
Mental Deficiency ◽  
Low Grade ◽  
High Grade ◽  
Single Factor ◽  
Important Distinction ◽  
Differential Fertility ◽  
The People ◽  
Hereditary Factors ◽  
The Individual

Mr. Caradoc Jones this morning emphasized very clearly indeed the important distinction between high and low grade mental deficiency. He showed us some very striking figures suggesting, not that heredity is not involved in both, but that it is a different sort of heredity. It always seems to me that in considering this and related matters the analogy of stature is a helpful one. Many of us remember those posters of the last war but one, which said “Your King and Country Need YOU,” coupled with the statement that “You” had to be 5 ft. 4 in. high—a standard which went down afterwards. If one rejects for any purpose a segment of the population on a measurement of this kind one is rejecting people for very different reasons. The arbitrary standard cuts off, of course, the dwarfs; the achondroplasics, the midgets, the cretins, the rachitic dwarfs, and so on; but it cuts off far more of those who are simply short. In causation we can normally expect the dwarf's condition to be due to hereditary factors, actually a single factor in achondroplasia; or it may be something environmental, as in the rachitic dwarfs or the cretins, but when we come to the people who are just short, it has been shown fairly conclusively that in a civilized community in which the standard of nutrition is adequate, at least 90 per cent. of the differences are due to heredity; but it is a different sort of heredity. We have a whole host of genetic factors, each one of which has a small effect; but the effect is cumulative; some factors make for greater stature, some for smaller, and it is on the sum total received from the parents that the stature of the individual depends.

scholarly journals KDM6A mediated expression of the long noncoding RNA DINO causes TP53 tumor suppressor stabilization in Human Papillomavirus type 16 E7 expressing cells

2020 ◽  
Author(s):  
Surendra Sharma ◽  
Karl Munger
Keyword(s):  
Cell Death ◽  
Tumor Suppressor ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Critical Role ◽  
Metabolic Stress ◽  
Dominant Negative ◽  
Missing Link ◽  
Hpv16 E6 ◽  
E6 And E7

ABSTRACTHPV16 E7 has long been noted to stabilize the TP53 tumor suppressor. However, the molecular mechanism of TP53 stabilization by HPV16 E7 has remained obscure and can occur independent of E2F regulated MDM2 inhibitor, p14ARF. Here, we report that the Damage Induced Noncoding (DINO) lncRNA (DINOL) is the missing link between HPV16 E7 and increased TP53 levels. DINO levels are decreased in cells where TP53 is inactivated, either by HPV16 E6, expression of a dominant negative TP53 minigene or by TP53 depletion. DINO levels are increased in HPV16 E7 expressing cells. HPV16 E7 causes increased DINO expression independent of RB1 degradation and E2F1 activation. Similar to the adjacent CDKN1A locus, DINO expression is regulated by the histone demethylase, KDM6A. DINO stabilizes TP53 in HPV16 E7 expressing cells and as a TP53 transcriptional target, DINO levels further increase. Similar to other oncogenes such as adenovirus E1A or MYC, HPV16 E7 expressing cells are sensitized to cell death under conditions of metabolic stress and in the case of E7, this has been linked to TP53 activation. Consistent with earlier studies, we show that HPV16 E7 expressing keratinocytes are highly sensitive to metabolic stress induced by the antidiabetic drug, metformin. Metformin sensitivity of HPV16 E7 expressing cells is rescued by DINO depletion. This work identifies DINO as a critical mediator TP53 stabilization and activation in HPV16 E7 expressing cells.IMPORTANCEViral oncoproteins, including HPV16 E6 and E7 have been instrumental in elucidating the activities of cellular signaling networks including those governed by the TP53 tumor suppressor. Our study demonstrates that the long noncoding RNA DINO is the long sought missing link between HPV16 E7 and elevated TP53 levels. Importantly, the TP53 stabilizing DINO plays a critical role in the predisposition of HPV16 E7 expressing cells to cell death under metabolic stress conditions from metformin treatment.

scholarly journals A Radiomics nomogram for preoperative predicting recurrence of low grade gliomas based on multiparametric MRI

2021 ◽  
Author(s):  
Zhenhua Wang ◽  
Xinlan Xiao ◽  
Zhaotao Zhang ◽  
Keng He ◽  
Peipei Pang ◽  
...  
Keyword(s):  
Multivariate Logistic Regression Analysis ◽  
Low Grade ◽  
Training Set ◽  
Decision Curve Analysis ◽  
Logistic Analysis ◽  
Contrast Enhanced ◽  
Fluid Attenuated Inversion Recovery ◽  
Validation Set ◽  
The Individual ◽  
Good Agreement

Abstract Objective To develop a radiomics nomogram to predict the recurrence of Low grade glioma(LGG) after their first surgery; Methods A retrospective analysis of pathological, clinical and Magnetic resonance image(MRI) of LGG patients who underwent surgery and had a recurrence between 2017 and 2020 in our hospital was performed. After a rigorous selection,64 patients were eligible and enrolled in the study(22 cases were with recurrent gliomas),which was randomly assigned in a 7:3 ratio to either the training set and validation set; T1WI,T2WI fluid-attenuated-inversion-recovery(T2WI-FLAIR) and contrast-enhanced T1-weighted(T1CE) sequences, 396 radiomics features were extracted from each image sequence, minimum-redundancy maximum-relevancy(mRMR) alone or combining with univariate logistic analysis were used for features screening, the screened features were performed by multivariate logistic regression analysis and developed a predictive model both in training set and validation set; Receiver operating characteristic(ROC) curve, calibration curve, and decision curve analysis(DCA) were used to assess the performance of each model. Results The radiomics nomogram derived from three MRI sequence yielded an ideal performance than the individual ones, the AUC in the training set and validation set were 0.966 and 0.93 respectively, 95% confidence interval(95%CI) were 0.949-0.99 and 0.905-0.973 respectively; the calibration curves indicated good agreement between the predictive and the actual probability. The DCA demonstrated that a combination of three sequences had more favorable clinical predictive value than single sequence imaging. Conclusion Our multiparametric radiomics nomogram could be an efficient and accurate tool for predicting the recurrence of LGG after its first resection.

Expression of bacterial Rubisco genes in Escherichia coli

1986 ◽  
Vol 313 (1162) ◽  
pp. 433-445 ◽  
Keyword(s):  
Escherichia Coli ◽  
Rhodospirillum Rubrum ◽  
Active Form ◽  
Amino Acid Residues ◽  
Structural Genes ◽  
Physico Chemical ◽  
Chemical Studies ◽  
The Individual ◽  
Very High

The structural genes for three forms of Rubisco have been isolated from bacteria and introduced into various plasmids. Apart from details of the sequences which have been obtained from these constructs, they are now being exploited for mutagenesis to determine the identity and specific function of the individual amino acid residues that compose the active site. These methods have been applied to a plasmid that contains the structural gene for the simplest form of Rubisco from Rhodospirillum rubrum to obtain mutant enzymes with altered activity. The construct pRR2119 is also expressed to very high levels in Escherichia coli and enough recombinant protein of both the wild-type and m utant enzymes can be obtained for detailed physico-chemical studies. Other vectors have now been constructed, containing the genes of prokaryotic Rubisco that assemble into an active form I enzyme. The levels of expression are acceptable and the product is similar to the authentic enzyme. These constructs are now being used for mutagenesis in vitro to attempt to alter the relative rates of the oxygenase and carboxylase activities.

scholarly journals Delivery of a nutritional prescription by enteral tube feeding in children with chronic kidney disease stages 2–5 and on dialysis—clinical practice recommendations from the Pediatric Renal Nutrition Taskforce

2020 ◽  
Vol 36 (1) ◽  
pp. 187-204
Author(s):  
Lesley Rees ◽  
◽  
Vanessa Shaw ◽  
Leila Qizalbash ◽  
Caroline Anderson ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Growth Parameters ◽  
Tube Feeding ◽  
Low Grade ◽  
Enteral Tube Feeding ◽  
Practice Recommendations ◽  
The Individual ◽  
Disease Stages

AbstractThe nutritional prescription (whether in the form of food or liquid formulas) may be taken orally when a child has the capacity for spontaneous intake by mouth, but may need to be administered partially or completely by nasogastric tube or gastrostomy device (“enteral tube feeding”). The relative use of each of these methods varies both within and between countries. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, has developed clinical practice recommendations (CPRs) based on evidence where available, or on the expert opinion of the Taskforce members, using a Delphi process to seek consensus from the wider community of experts in the field. We present CPRs for delivery of the nutritional prescription via enteral tube feeding to children with chronic kidney disease stages 2–5 and on dialysis. We address the types of enteral feeding tubes, when they should be used, placement techniques, recommendations and contraindications for their use, and evidence for their effects on growth parameters. Statements with a low grade of evidence, or based on opinion, must be considered and adapted for the individual patient by the treating physician and dietitian according to their clinical judgement. Research recommendations have been suggested. The CPRs will be regularly audited and updated by the PRNT.

Sign in / Sign up

Export Citation Format

Share Document