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Epidemiological and functional implications of molecular variants of human papillomavirus
Sichero, L.;Villa, L.L.;
Brazilian Journal of Medical and Biological Research , 2006, DOI: 10.1590/S0100-879X2006000600002
Abstract: human papillomavirus genomes are classified into molecular variants when they present more than 98% of similarity to the prototype sequence within the l1 gene. comparative nucleotide sequence analyses of these viruses have elucidated some features of their phylogenetic relationship. in addition, human papillomavirus intratype variability has also been used as an important tool in epidemiological studies of viral transmission, persistence and progression to clinically relevant cervical lesions. until the present, little has been published concerning the functional significance of molecular variants. it has been shown that nucleotide variability within the long control region leads to differences in the binding affinity of some cellular transcriptional factors and to the enhancement of the expression of e6 and e7 oncogenes. furthermore, in vivo and in vitro studies revealed differences in e6 and e7 biochemical and biological properties among molecular variants. nevertheless, further correlation with additional functional information is needed to evaluate the significance of genome intratypic variability. these results are also important for the development of vaccines and to determine the extent to which immunization with l1 virus-like particles of one variant could induce antibodies that cross-neutralize other variants.
Epidemiological and functional implications of molecular variants of human papillomavirus  [cached]
Sichero L.,Villa L.L.
Brazilian Journal of Medical and Biological Research , 2006,
Abstract: Human papillomavirus genomes are classified into molecular variants when they present more than 98% of similarity to the prototype sequence within the L1 gene. Comparative nucleotide sequence analyses of these viruses have elucidated some features of their phylogenetic relationship. In addition, human papillomavirus intratype variability has also been used as an important tool in epidemiological studies of viral transmission, persistence and progression to clinically relevant cervical lesions. Until the present, little has been published concerning the functional significance of molecular variants. It has been shown that nucleotide variability within the long control region leads to differences in the binding affinity of some cellular transcriptional factors and to the enhancement of the expression of E6 and E7 oncogenes. Furthermore, in vivo and in vitro studies revealed differences in E6 and E7 biochemical and biological properties among molecular variants. Nevertheless, further correlation with additional functional information is needed to evaluate the significance of genome intratypic variability. These results are also important for the development of vaccines and to determine the extent to which immunization with L1 virus-like particles of one variant could induce antibodies that cross-neutralize other variants.
Molecular diagnosis of human papillomavirus in the development of cervical cancer
Gutiérrez-Xicoténcatl,Lourdes; Plett-Torres,Tanya; Madrid-González,Claudia L; Madrid-Marina,Vicente;
Salud Pública de México , 2009, DOI: 10.1590/S0036-36342009000900014
Abstract: cervical cancer (cc) is a major public health problem in developing countries and its most significant etiological risk factor is infection by the human papillomavirus (hpv). the main approach to date for the prevention of cc has been through screening programs, using the cervical smear (pap test) to detect precursory lesions. the sensitivity and specificity of the pap smear depend on the skills of the observer to recognize and classify a variety of cellular abnormalities. the development of early diagnoses to detect hpv infection has been a problem as cytology and colposcopy identify the lesion at an advanced stage. therefore, molecular approaches have become more successful for early cc diagnosis. these molecular techniques recognize hpv dna sequences by dna hybridization, pcr-rflp, hybrid capture and reverse line blot systems. unfortunately, these systems cannot determine whether the hpv infection is active, latent or persistent. thus, immunological techniques such as western blot and elisa have been designed to follow the immune response against the virus, and they can also be used to identify the stage of the infection. several companies have developed, manufactured and merchandised gene-based testing systems for the screening, monitoring and diagnosis of hpv. our review and comments focus on the critical analysis of existing products and their use in clinical practice as well as on immunological systems used mainly in research, but that may be applied in large population screening programs.
Molecular epidemiology and pathogenic potential of underdiagnosed human papillomavirus types
Stefano Menzo, Andrea Ciavattini, Patrizia Bagnarelli, Katia Marinelli, Stefano Sisti, Massimo Clementi
BMC Microbiology , 2008, DOI: 10.1186/1471-2180-8-112
Abstract: In this study, we tested 6,335 consecutive clinical samples, most of them from Italian patients with cytological abnormalities. The samples, collected in 2000–2007, were analyzed using PCR amplification of a 173–206 bp (depending on HPV type) conserved region in the L1 open reading frame, restriction endonuclease analysis and, where required, sequence analysis for type determination. Analysis of a smaller male sample and long term follow-up of a few female subjects was also performed. A total of 2,161 samples tested positive for HPV DNA (32.1%); 21.3% of them were mixed infections. Overall, 59 known and 2 unknown HPV types were detected. Their relative prevalence was calculated; notably, types not clearly identifiable using the most common commercial method accounted for 36% of infections. Clinical findings associated with the underdiagnosed types ranged from H-SIL to low-grade abnormalities, although none of these infections resulted in invasive cancer.Given the high prevalence of some underdiagnosed HPV types in the population (principally HPV53, HPV66, HPV84, and HPV87) and their frequent association with cytological abnormalities, techniques capable of detecting and typing them would prove extremely useful.Human papillomavirus (HPV) infections of the genital tract are highly prevalent in the population worldwide; indeed, it is estimated that the great majority of sexually active individuals become infected with one or more of these viruses in their lifetimes. Most conditions are transient and are cleared without consequences. However, in a small proportion of cases, infections associated with the so-called high-risk (HR) HPV types can persist in typical lesions with a high viral load for years, and a fraction of such lesions eventually progress to invasive malignancies. Although many cofactors normally concur in this process, the HPV type implicated (the type-specific viral oncogenes) and the inability of the immune system to clear the infection are by far the m
Molecular Diagnosis of Human Papillomavirus: Comparison Between Cervical and Vaginal Sampling  [PDF]
Ramzi R. Finan,Noha Irani-Hakime,Hala Tamim,Wassim Y. Almawi
Infectious Diseases in Obstetrics and Gynecology , 2001, DOI: 10.1155/s1064744901000217
Abstract: Background: Human papillomavirus (HPV) is the most significant cause of cervical cancer. In view of the number of drawbacks associated with endocervical sampling, the gold standard for HPV detection, this study examined the utility and specificity of vaginal sampling as an alternative for endocervical sampling for the routine detection of HPV.
Assessing protein stability of the dimeric DNA-binding domain of E2 human papillomavirus 18 with molecular dynamics
Isea, Raúl;Ramírez, José Luis;Hoebeke, Johan;
Memórias do Instituto Oswaldo Cruz , 2010, DOI: 10.1590/S0074-02762010000200002
Abstract: the objective of this study is to understand the structural flexibility and curvature of the e2 protein of human papillomavirus type 18 using molecular dynamics (6 ns). e2 is required for viral dna replication and its disruption could be an anti-viral strategy. e2 is a dimer, with each monomer folding into a stable open-faced β-sandwich. we calculated the mobility of the e2 dimer and found that it was asymmetric. these different mobilities of e2 monomers suggest that drugs or vaccines could be targeted to the interface between the two monomers.
Analysis of molecular biology techniques for the diagnosis of human papillomavirus infection and cervical cancer prevention
Carestiato, Fernanda Nahoum;Silva, Kátia Cristina da;Balthazar, Daniela Signorelli;Silva, Licínio;Marinho, Marisa;Oliveira, Ledy Horto dos Santos;Cavalcanti, Silvia Maria Baeta;
Revista da Sociedade Brasileira de Medicina Tropical , 2006, DOI: 10.1590/S0037-86822006000500002
Abstract: the objective of the present study was to evaluate the usefulness of molecular methodologies to access human papillomavirus genome in the genital tract. samples from 136 women aged 17 to 52 years old obtained from the dr. sérgio franco laboratories between 2000 and 2001, were analyzed by the hybrid capture assay and amplified by pcr with generic primers my09/my11 and specific primers for types 16, 18, 31, 33, 35, 58. viral genome was detected in 71.3% of the samples by hybrid capture and 75% by amplification. when cytopathology was used as a reference method for screening lesions, hybrid capture (p=0) and amplification (p=0.002) presented positive association. the 3 methods showed absolute agreement when cytopathology confirmed papillomavirus infection and high grade intraepithelial lesion. disagreements occurred for 10 cases: seven inflammatory cases positive by pcr and negative for hybrid capture and 3 low squamous intraepithelial lesions positive for hybrid capture but negative for amplification. in conclusion, hybrid capture was shown to be sensitive and specific enough for use in clinical routines. moreover, the evaluation of viral load values obtained by this method were shown to be related to the severity of the lesion and merit further studies to analyze the possible association with risk of progression to malignancy.
Principal manifolds and graphs in practice: from molecular biology to dynamical systems  [PDF]
A. N. Gorban,A. Zinovyev
Computer Science , 2010, DOI: 10.1142/S0129065710002383
Abstract: We present several applications of non-linear data modeling, using principal manifolds and principal graphs constructed using the metaphor of elasticity (elastic principal graph approach). These approaches are generalizations of the Kohonen's self-organizing maps, a class of artificial neural networks. On several examples we show advantages of using non-linear objects for data approximation in comparison to the linear ones. We propose four numerical criteria for comparing linear and non-linear mappings of datasets into the spaces of lower dimension. The examples are taken from comparative political science, from analysis of high-throughput data in molecular biology, from analysis of dynamical systems.
Study on Antibody-Virus Interaction using Molecular Dynamics: Two Dimensional Simulation on Immunoglobulin Reaction against Human Papillomavirus  [PDF]
Luman Haris,Sony Suhandono,Siti Nurul Khotimah,Freddy Haryanto,Sparisoma Viridi
Quantitative Biology , 2013,
Abstract: Human Papillomavirus (HPV) has been known as one of the cause of virus-induced cancer such as cervical cancer and carcinoma. Among other types of cancer, this type has higher chance in being prevented earlier. The main idea is to eradicate the virus as soon as it enters the body by marking it with antibodies; signaling the immune system to dispose of it. However, the antibodies must be trained to recognize the virus. They can be trained by inserting an object similar to the virus allowing them to learn to recognize and surround the inserted object. In response to this, molecular dynamics simulation was chosen to study the antibody-virus interaction. In this work, two-dimensional case that involves HPV and immunoglobulin (Ig) was studied and observed. Two types of objects will be defined; one stands for HPV while another stands for antibodies. The interaction between the two objects will be governed by two forces; Coulomb force and repulsive contact force. Through the definition of some rules and condition, the antibodies' motion was observed. The influence of antibody concentration, and the antibody's type and their appearance sequence were observed both quantitatively and visually. Keywords: antibody-virus interaction, molecular dynamics, HPV, immunoglobulin.
Detecting genomic signatures of natural selection with principal component analysis: application to the 1000 Genomes data  [PDF]
Nicolas Duforet-Frebourg,Keurcien Luu,Guillaume Laval,Eric Bazin,Michael G. B. Blum
Quantitative Biology , 2015,
Abstract: To characterize natural selection, various analytical methods for detecting candidate genomic regions have been developed. We propose to perform genome-wide scans of natural selection using principal component analysis. We show that the common Fst index of genetic differentiation between populations can be viewed as a proportion of variance explained by the principal components. Considering the correlations between genetic variants and each principal component provides a conceptual framework to detect genetic variants involved in local adaptation without any prior definition of populations. To validate the PCA-based approach, we consider the 1000 Genomes data (phase 1) after removal of recently admixed individuals resulting in 850 individuals coming from Africa, Asia, and Europe. The number of genetic variants is of the order of 36 millions obtained with a low-coverage sequencing depth (3X). The correlations between genetic variation and each principal component provide well-known targets for positive selection (EDAR, SLC24A5, SLC45A2, DARC), and also new candidate genes (APPBPP2, TP1A1, RTTN, KCNMA, MYO5C) and non-coding RNAs. In addition to identifying genes involved in biological adaptation, we identify two biological pathways involved in polygenic adaptation that are related to the innate immune system (beta defensins) and to lipid metabolism (fatty acid omega oxidation). An additional analysis of European data shows that a genome scan based on PCA retrieves classical examples of local adaptation even when there are no well-defined populations. PCA-based statistics, implemented in the PCAdapt R package and the PCAdapt open-source software, retrieve well-known signals of human adaptation, which is encouraging for future whole-genome sequencing project, especially when defining populations is difficult.
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