Genetic variability in the major capsid L1 protein of human papillomavirus type 16 (HPV-16) and 18 (HPV-18)

2011 ◽  
Vol 11 (8) ◽  
pp. 2119-2124 ◽  
Author(s):  
E. Frati ◽  
S. Bianchi ◽  
D. Colzani ◽  
A. Zappa ◽  
G. Orlando ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Genetic Variability ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein ◽  
Hpv 18

scholarly journals PDZRN3/LNX3 Is a Novel Target of Human Papillomavirus Type 16 (HPV-16) and HPV-18 E6

2014 ◽  
Vol 89 (2) ◽  
pp. 1439-1444 ◽  
Author(s):  
Miranda Thomas ◽  
Lawrence Banks
Keyword(s):  
Human Papillomavirus ◽  
Binding Motif ◽  
Dependent Manner ◽  
Hpv 16 ◽  
Cellular Targets ◽  
Ubiquitin Protein Ligase ◽  
Human Papillomavirus Type 16 ◽  
Hpv E6 ◽  
Novel Target ◽  
Hpv 18

High-risk human papillomavirus (HPV) E6 proteins have a C-terminal PDZ binding motif through which they bind, and target for proteasome-mediated degradation, a number of PDZ-containing cellular targets. Recent studies have suggested that the RING-containing ubiquitin-protein ligase PDZRN3 might also be an HPV E6 target. In this analysis, we show that HPV-16 and HPV-18 E6 can target PDZRN3 in a PDZ- and proteasome-dependent manner and provide a connection between the HPV life cycle and differentiation-related STAT signaling.

scholarly journals Production of Human Papillomavirus Type 16 L1 Virus-Like Particles by Recombinant Lactobacillus casei Cells

2006 ◽  
Vol 72 (1) ◽  
pp. 745-752 ◽  
Author(s):  
Karina Araujo Aires ◽  
Aurora Marques Cianciarullo ◽  
Sylvia Mendes Carneiro ◽  
Luisa Lina Villa ◽  
Enrique Boccardo ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Lactobacillus Casei ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hpv 16 ◽  
Virus Like Particles ◽  
Human Papillomavirus Type 16 ◽  
Common Causes ◽  
Electron Microscopy Analysis ◽  
Microscopy Analysis ◽  
L1 Protein

ABSTRACT Infections with human papillomavirus type 16 (HPV-16) are closely associated with the development of human cervical carcinoma, which is one of the most common causes of cancer death in women worldwide. At present, the most promising vaccine against HPV-16 infection is based on the L1 major capsid protein, which self-assembles in virus-like particles (VLPs). In this work, we used a lactose-inducible system based on the Lactobacillus casei lactose operon promoter (plac) for expression of the HPV-16 L1 protein in L. casei. Expression was confirmed by Western blotting, and an electron microscopy analysis of L. casei expressing L1 showed that the protein was able to self-assemble into VLPs intracellularly. The presence of conformational epitopes on the L. casei-produced VLPs was confirmed by immunofluorescence using the anti-HPV-16 VLP conformational antibody H16.V5. Moreover, sera from mice that were subcutaneously immunized with L. casei expressing L1 reacted with Spodoptera frugiperda-produced HPV-16 L1 VLPs, as determined by an enzyme-linked immunosorbent assay. The production of L1 VLPs by Lactobacillus opens the possibility for development of new live mucosal prophylactic vaccines.

scholarly journals Influence of Codon Bias on Heterologous Production of Human Papillomavirus Type 16 Major Structural Protein L1 in Yeast

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Milda Norkiene ◽  
Alma Gedvilaite
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Codon Bias ◽  
Heterologous Gene Expression ◽  
Heterologous Production ◽  
Structural Protein ◽  
Hpv 16 ◽  
Major Structural Protein ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein

Heterologous gene expression is dependent on multistep processes involving regulation at the level of transcription, mRNA turnover, protein translation, and posttranslational modifications. Codon bias has a significant influence on protein yields. However, sometimes it is not clear which parameter causes observed differences in heterologous gene expression as codon adaptation typically optimizes many sequence properties at once. In the current study, we evaluated the influence of codon bias on heterologous production of human papillomavirus type 16 (HPV-16) major structural protein L1 in yeast by expressing five variants of codon-modified open reading frames (OFRs) encoding HPV-16 L1 protein. Our results showed that despite the high toleration of various codons used throughout the length of the sequence of heterologously expressed genes in transformed yeast, there was a significant positive correlation between the gene's expression level and the degree of its codon bias towards the favorable codon usage. The HPV-16 L1 protein expression in yeast can be optimized by adjusting codon composition towards the most preferred codon adaptation, and this effect most probably is dependent on the improved translational elongation.

scholarly journals The Chromatin Structure of the Long Control Region of Human Papillomavirus Type 16 Represses Viral Oncoprotein Expression

1999 ◽  
Vol 73 (3) ◽  
pp. 1918-1930 ◽  
Author(s):  
Walter Stünkel ◽  
Hans-Ulrich Bernard
Keyword(s):  
Human Papillomavirus ◽  
Control Region ◽  
Replication Origin ◽  
Chromatin Organization ◽  
Long Control Region ◽  
Promoter Elements ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
Hpv 18

ABSTRACT The long control region (LCR) of human papillomavirus type 16 (HPV-16) has a size of 850 bp (about 12% of the viral genome) and regulates transcription and replication of the viral DNA. The 5′ segment of the LCR contains transcription termination signals and a nuclear matrix attachment region, the central segment contains an epithelial cell-specific enhancer, and the 3′ segment contains the replication origin and the E6 promoter. Here we report observations on the chromatin organization of this part of the HPV-16 genome. Treatment of the nuclei of CaSki cells, a cell line with 500 intrachromosomal copies of HPV-16, with methidiumpropyl-EDTA-Fe(II) reveals nucleosomes in specific positions on the LCR and the E6 and E7 genes. One of these nucleosomes, which we termed Ne, overlaps with the center of the viral enhancer, while a second nucleosome, Np16, overlaps with the replication origin and the E6 promoter. The two nucleosomes become positioned on exactly the same segments after in vitro assembly of chromatin on the cloned HPV-16 LCR. Primer extension mapping of DNase I-cleaved chromatin revealed Np16 to be positioned centrally over E6 promoter elements, extending into the replication origin. Ne covers the center of the enhancer but leaves an AP-1 site, one of the strongestcis-responsive elements of the enhancer, unprotected. Np16, or a combination of Np16 and Ne, represses the activity of the E6 promoter during in vitro transcription of HPV-16 chromatin. Repression is relieved by addition of Sp1 and AP-1 transcription factors. Sp1 alters the structure of Np16 in vitro, while no changes can be observed during the binding of AP-1. HPV-18, which has a similar arrangement ofcis-responsive elements despite its evolutionary divergence from HPV-16, shows specific assembly in vitro of a nucleosome, Np18, over the E1 binding site and E6 promoter elements but positioned about 90 bp 5′ of the position of Np16 on the homologous HPV-16 sequences. The chromatin organization of the HPV-16 and HPV-18 genomes suggests important regulatory roles of nucleosomes during the viral life cycle.

Human Papillomavirus Type 16 Exists in Bacteria Isolated from Cervical Cancer Biopsies

2009 ◽  
Vol 37 (4) ◽  
pp. 1065-1074 ◽  
Author(s):  
Zhenghai Ma ◽  
Lihong Liu ◽  
Fuchun Zhang ◽  
Meng Yu ◽  
Kai Wang ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Bacterial Cells ◽  
Bacterial Strains ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
Reverse Transcription Pcr ◽  
Bacterial Rna ◽  
L1 Protein

This study investigated the association between infectious microbes and persistent infection with human papillomavirus type 16 (HPV-16) in cervical cancer. Bacterial strains (identified as Enterococcus, Staphylococcus, Bacillus and Corynebacterium, based on their partial 16S rDNA sequence) were HPV-16 positive from 12 out of 14 cervical cancer biopsies. Total DNA was isolated from the four bacterial strains, and HPV-16 genes and genome were detected using polymerase chain reaction (PCR) and Southern blotting. RNA transcripts for HPV-16 E6 and L1 genes were detected in total bacterial RNA samples using reverse transcription-PCR, and HPV-16 L1 protein expression was detected in bacterial cells by Western blotting and immunocolloidal gold electron microscopy. The presence of virus particles in bacterial cells was demonstrated by transmission electron microscopy. The results suggest that bacteria carrying HPV-16 could provide a potential explanation for how infectious microbes contribute to the progression from HPV-16 infection to cervical cancer.

scholarly journals Nasal Immunization of Mice with Human Papillomavirus Type 16 (HPV-16) Virus-Like Particles or with the HPV-16 L1 Gene Elicits Specific Cytotoxic T Lymphocytes in Vaginal Draining Lymph Nodes

1999 ◽  
Vol 73 (11) ◽  
pp. 9063-9071 ◽  
Author(s):  
Catherine Dupuy ◽  
Dominique Buzoni-Gatel ◽  
Antoine Touzé ◽  
Daniel Bout ◽  
Pierre Coursaget
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
Immune Responses ◽  
Self Assembly ◽  
Genital Tract ◽  
Hpv 16 ◽  
Virus Like Particles ◽  
Mammalian Expression ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein

ABSTRACT Human papillomavirus type 16 (HPV-16) infects the genital tract and is closely associated with the development of cervical cancer. HPV-16 initiates infection at the genital mucosal surface; thus, mucosal immune responses are likely to contribute to defense against HPV-16 infection. However, little information is available regarding the induction of immune responses in the genital tract mucosa. In this study, we evaluated the potential of intranasally administered papillomavirus vaccines to elicit both systemic and vaginal immune responses. HPV-16 virus-like particles (VLPs) produced by self-assembly of L1 protein and the HPV-16 L1 gene cloned into a mammalian expression vector were used as vaccines. Intranasally administered VLPs induced serum immunoglobulin G (IgG) and vaginal IgA secretory antibodies. Very weak serum IgG and vaginal IgA responses were found after DNA immunization. Both splenic and vaginal lymphocytes could be activated by intranasal immunization with VLPs and the HPV-16 L1 gene. Activated CD4+ Th1-like T cells were shown to synthesize gamma interferon, and activated CD8+ T cells were demonstrated to be cytotoxic.

scholarly journals The L1 Major Capsid Protein of Human Papillomavirus Type 16 Variants Affects Yield of Virus-Like Particles Produced in an Insect Cell Expression System

1998 ◽  
Vol 36 (7) ◽  
pp. 2046-2051 ◽  
Author(s):  
Antoine Touze ◽  
Slimane El Mehdaoui ◽  
Pierre-Yves Sizaret ◽  
Christine Mougin ◽  
Nubia Muñoz ◽  
...  
Keyword(s):  
Amino Acids ◽  
Human Papillomavirus ◽  
Expression System ◽  
The Philippines ◽  
Serological Tests ◽  
Hpv 16 ◽  
Virus Like Particles ◽  
Human Papillomavirus Type 16 ◽  
Amino Acid Region ◽  
L1 Protein

The L1 major capsid proteins of six human papillomavirus type 16 (HPV-16) strains were expressed in insect cells by using recombinant baculoviruses. Virus-like particles (VLPs) which appeared similar to empty virions were identified by electron microscopy for all HPV strains investigated. However, the yield of VLPs produced varied in a range from 1 to 79 depending on the HPV-16 strain. The L1 proteins of these strains differed by up to 15 amino acids from the L1 protein of the prototype HPV-16 strain. Mutations in the amino acid region from residues 83 to 97 seemed to affect the level of expression of the L1 protein. These results are important when considering the development of HPV vaccines and serological tests. They indicate that strains inducing high levels of VLP production must be selected for the development of vaccines. Moreover, the L1 proteins of all strains investigated were able to bind with DNA. We also investigated the seroreactivities of VLPs derived from three different HPV-16 strains from Algeria, Senegal, and the Philippines by testing sera from women from 11 countries in immunoglobulin G-specific enzyme-linked immunosorbent assays. We observed a strong correlation between the reactivities of the three different VLP variants, independent of the geographical origin of the sera investigated. These results indicate that the three strains investigated are serologically cross-reactive despite the fact that their L1 proteins differ in 14 amino acids and suggest that VLPs derived from only one HPV-16 strain could be sufficient for the development of an HPV-16 vaccine and anti-HPV-16 tests.

scholarly journals Complementation of a p300/CBP defective-binding mutant of adenovirus E1a by human papillomavirus E6 proteins

2002 ◽  
Vol 83 (4) ◽  
pp. 829-833 ◽  
Author(s):  
Agnieszka Bernat ◽  
Paola Massimi ◽  
Lawrence Banks
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Cell Transformation ◽  
Deficient Mutant ◽  
Hpv 16 ◽  
Adenovirus E1a ◽  
Human Papillomavirus Type 16 ◽  
Hpv E6 ◽  
E6 Protein ◽  
Hpv 18

Previous studies have shown that the human papillomavirus type 16 (HPV-16) E6 protein binds to p300/CBP and abrogates its transcriptional co-activator function. However, there is little information on the biological consequences of this interaction and discrepancy as to whether the interaction is high-risk E6 specific or not. We performed a series of studies to compare the interactions of HPV-18 and HPV-11 E6 with p300, and showed that both high- and low- risk E6 proteins bind p300. In addition, using a transformation-deficient mutant of adenovirus E1a, which cannot interact with p300, we demonstrated that HPV-16, HPV-18 and, to a lesser extent, HPV-11 E6, can complement this mutant in cell transformation assays. In contrast, a mutant of HPV-16 E6 which does not bind p300 failed to rescue the E1a mutant. These results suggest that the E6–p300 interaction may be important for the ability of HPV E6 to contribute towards cell transformation.

PECULIARITIES OF PAPILLOMAVIRUS GENOTYPING IN PATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA

2020 ◽  
pp. 104-111
Author(s):  
N.A. Shmakova ◽  
G.N. Chistyakova ◽  
I.N. Kononova ◽  
I.I. Remizova
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Viral Load ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
The World ◽  
Intraepithelial Lesions ◽  
Hpv 18

Recently, there has been a steady growth of cervical cancer all over the world, especially in Russia. Patients with cervical cancer have become much younger. At the same time, the human papillomavirus is not only the main factor in the neoplastic process, but it is also one of the most common sexually transmitted infections in the world. The aim of the paper is to assess the prevalence and characteristics of human papillomavirus genotypes in patients with cervical intraepithelial neoplasia. Materials and Methods. During the periodic screening we examined 213 women of a reproductive age with HPV infection. All patients underwent liquid-based cytology and human papillomavirus genotyping by polymerase chain reaction. Results. We revealed that the prevalence of cervical intraepithelial neoplasia among women with papillomavirus infection was 80.3 % (n=171). According to human papillomavirus genotyping, HPV 16 (38 %) and HPV 33 (32 %) prevailed. We also observed positive high correlation between high-grade squamous intraepithelial lesions (HSIL) and HPV 18 (r=+0.759, p=0.001), a negative mean correlation between HPV 45 and low-grade squamous intraepithelial lesions (LSIL) (r=-0.643, p=0.002). A cohort of patients with severe intraepithelial cervical lesions demonstrated high viral load rates. Conclusion. According to the results obtained, we established the dominance of HPV 16 and HPV 33 genotypes in cervical intraepithelial neoplasia. There were significant differences between HSIL and LSIL patients with HPV 18 and HPV 45. There was also a correlation between an increase in the viral load with the severity of the pathological process. Keywords: human papillomavirus, intraepithelial cervical neoplasms, cervical cancer. В последние годы в мире, особенно в России, наблюдается неуклонный рост и «омолаживание» рака шейки матки. При этом вирус папилломы человека является не только основным фактором прогрессирования неопластического процесса, но и одной из наиболее распространенных инфекций, предаваемых половым путем, в мире. Цель. Оценить распространенность и характеристику генотипов папилломавирусной инфекции у пациенток с цервикальными интраэпителиальными неоплазиями. Материалы и методы. Проведено обследование 213 пациенток репродуктивного возраста с ВПЧ-инфекцией, пришедших на профилактический осмотр. Всем женщинам было выполнено цитологическое исследование жидкостным методом и генотипирование вируса папилломы человека методом полимеразной цепной реакции. Результаты. Распространенность цервикальных интраэпителиальных неоплазий среди женщин с папилломавирусной инфекцией составила 80,3 % (171 пациентка). Согласно данным генотипирования вируса папилломы человека превалировал 16-й (38 %) и 33-й типы (32 %). Выявлена положительная высокая корреляционная связь между цервикальными неоплазиями высокой степени онкогенного риска (HSIL) и 18-м типом ВПЧ-инфекции (r=+0,759 при р=0,001), отрицательная средняя корреляционная связь 45-го типа ВПЧ с низкой степенью онкогенного риска (LSIL) (r=-0,643 при р=0,002). Продемонстрированы высокие показатели вирусной нагрузки в когорте пациенток с тяжелыми внутриэпителиальными цервикальными поражениями. Выводы. По результатам полученных данных установлено доминирование 16-го и 33-го генотипов ВПЧ при цервикальных интраэпителиальных неоплазиях с наличием значимых различий между пациентами с HSIL и LSIL в отношении 18-го и 45-го типов, а также связь роста уровня вирусной нагрузки с увеличением степени тяжести патологического процесса. Ключевые слова: вирус папилломы человека, интраэпителиальные новообразования шейки матки, рак шейки матки.

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