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The Epstein-Barr virus (EBV) has been associated with gastric cancer (GC), one of the deadliest malignancies in Chile and the world. Little is known about Chilean EBV strains. This study aims to investigate the frequency and genetic diversity of EBV in GC in patients in southern Chile. To evaluate the prevalence of EBV in GC patients from the Chilean population, we studied 54 GC samples using the gold standard detection method of EBV-encoded small RNA (EBER). The EBV-positive samples were subjected to amplification and sequencing of the Epstein-Barr virus nuclear protein 3A (EBNA3A) gene to evaluate the genetic diversity of EBV strains circulating in southern Chile. In total, 22.2% of the GC samples were EBV-positive and significantly associated with diffuse-type histology (p = 0.003). Phylogenetic analyses identified EBV-1 and EBV-2 in the GC samples, showing genetic diversity among Chilean isolates. This work provides important information for an epidemiological follow-up of the different EBV subtypes that may cause GC in southern Chile.
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Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Herpesvirus Humano 4/genética , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/epidemiologia , Chile/epidemiologia , Filogenia , Variação GenéticaRESUMO
Fucoidans are sulphated polysaccharides that can be obtained from brown seaweed and marine invertebrates. They have anti-cancer properties, through their targeting of several signaling pathways and molecular mechanisms within malignant cells. This review describes the chemical structure diversity of fucoidans and their similarity with other molecules such as glycosaminoglycan, which enable them to participation in diverse biological processes. Furthermore, this review summarizes their influence on the development of metastasis and drug resistance, which are the main obstacles to cure cancer. Finally, this article discusses how fucoidans have been used in clinical trials to evaluate their potential synergy with other anti-cancer therapies.
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Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Polissacarídeos/uso terapêutico , Alga Marinha/química , Resistência a Medicamentos , Humanos , Biologia Marinha , Metástase NeoplásicaRESUMO
Photodynamic therapy (PDT) has been used to treat certain types of non-melanoma skin cancer with promising results. However, some skin lesions have not fully responded to this treatment, suggesting a potential PDT-resistant phenotype. Therefore, novel therapeutic alternatives must be identified that improve PDT in resistant skin cancer. In this study, we analyzed the cell viability, intracellular protoporphyrin IX (PpIX) content and subcellular localization, proliferation profile, cell death, reactive oxygen species (ROS) detection and relative gene expression in PDT-resistant HSC-1 cells. PDT-resistant HSC-1 cells show a low quantity of protoporphyrin IX and low levels of ROS, and thus a low rate of death cell. Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. On the other hand, epigallocatechin gallate catechin enhanced the MAL-PDT effect, increasing levels of protoporphyrin IX and ROS, and killing 100% of resistant cells. The resistant MAL-PDT model of skin cancer squamous cells (HSC-1) is a reliable and useful tool to understand PDT cytotoxicity and cellular response. These resistant cells were successfully sensitized with epigallocatechin gallate catechin. The in vitro epigallocatechin gallate catechin effect as an enhancer of MAL-PDT in resistant cells is promising in the treatment of difficult skin cancer lesions.
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Anticarcinógenos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Catequina/análogos & derivados , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Terapia Combinada/métodos , Fotoquimioterapia/métodos , Neoplasias Cutâneas/tratamento farmacológico , Ácido Aminolevulínico/análogos & derivados , Ácido Aminolevulínico/farmacologia , Carcinoma de Células Escamosas/radioterapia , Catequina/farmacologia , Morte Celular/efeitos da radiação , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/genética , Hipóxia Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ferroquelatase/genética , Ferroquelatase/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Fármacos Fotossensibilizantes/metabolismo , Protoporfirinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Cutâneas/radioterapia , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Estresse Fisiológico/efeitos da radiação , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Survivina/genética , Survivina/metabolismo , Simportadores/genética , Simportadores/metabolismoRESUMO
BACKGROUND: Ovarian cancer is a significant cancer-related cause of death in women worldwide. The most used chemotherapeutic regimen is based on carboplatin (CBDCA). However, CBDCA resistance is the main obstacle to a better prognosis. An in vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize cellular and molecular changes of induced CBDCA-resistant ovarian cancer cell line A2780. METHODS: The cell selection strategy used in this study was a dose-per-pulse method using a concentration of 100 µM for 2 h. Once 20 cycles of exposure to the drug were completed, the cell cultures showed a resistant phenotype. Then, the ovarian cancer cell line A2780 was grown with 100 µM of CBDCA (CBDCA-resistant cells) or without CBDCA (parental cells). After, a drug sensitivity assay, morphological analyses, cell death assays and a RNA-seq analysis were performed in CBDCA-resistant A2780 cells. RESULTS: Microscopy on both parental and CBDCA-resistant A2780 cells showed similar characteristics in morphology and F-actin distribution within cells. In cell-death assays, parental A2780 cells showed a significant increase in phosphatidylserine translocation and caspase-3/7 cleavage compared to CBDCA-resistant A2780 cells (P < 0.05 and P < 0.005, respectively). Cell viability in parental A2780 cells was significantly decreased compared to CBDCA-resistant A2780 cells (P < 0.0005). The RNA-seq analysis showed 156 differentially expressed genes (DEGs) associated mainly to molecular functions. CONCLUSION: CBDCA-resistant A2780 ovarian cancer cells is a reliable model of CBDCA resistance that shows several DEGs involved in molecular functions such as transmembrane activity, protein binding to cell surface receptor and catalytic activity. Also, we found that the Wnt/ß-catenin and integrin signaling pathway are the main metabolic pathway dysregulated in CBDCA-resistant A2780 cells.
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Antineoplásicos/farmacologia , Carboplatina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Ovarianas/genética , Transcriptoma/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Fenótipo , Análise de Sequência de RNA , Transdução de Sinais , Transcriptoma/genéticaRESUMO
PURPOSE: Cervical cancer is an important health issue among women worldwide. Cervical smear and human papillomavirus detection are the most used screening methods to detect preneoplastic and neoplastic lesions. However, as neither can predict cervical development, new markers are needed for this disease. ZNF516, a potential tumor suppressor gene, has been found altered in cervical cancer. The objective of this study was to determine ZNF516 immunohistochemistry frequency in cervical biopsies and its association with clinicopathological parameters, to evaluate its potential as marker in cervical lesions. METHODS: A retrospective series of 452 formalin-fixed, paraffin-embedded (FFPE) cervical biopsies, obtained between 2002 and 2007, were selected for immunohistochemistry of ZNF516, p16 and Ki-67 markers. Human papillomavirus genotyping was performed on 272 of these samples through reverse line blot assay. RESULTS: An inverse relation between ZNF516 expression and cervical lesions grade (P < 0.001) was observed, given this protein was found mainly expressed in normal tissues, while was decreased in cervical lesions. As expected, the proliferation markers p16 and Ki-67 were found highly expressed in cervical cancer compared to normal tissues, and inversely correlated to ZNF516 expression (P < 0.01). High oncogenic risk-Human papillomavirus presence also was related to the lack of ZNF516 expression in cervical lesions (P < 0.05), and the detection of these two parameters showed a high sensitivity (70.9%) for preneoplastic lesions detection. CONCLUSIONS: The loss of ZNF516 expression was found in cervical lesions, and its detection potentially could be used as a complementary marker of early diagnosis in cervical lesions.
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Proteínas de Ligação a DNA/análise , Infecções por Papillomavirus/complicações , Lesões Pré-Cancerosas/etiologia , Neoplasias do Colo do Útero/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias do Colo do Útero/química , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
We characterised and reported the first full-length genomes of Human T-cell Lymphotropic Virus Type 1 subgroup HTLV-1aD (CV21 and CV79). This subgroup is one of the major determinants of HTLV-1 infections in North and West Africa, and recombinant strains involving this subgroup have been recently demonstrated. The CV21 and CV79 strains from Cape Verde/Africa were characterised as pure HTLV-1aD genomes, comparative analyses including HTLV-1 subtypes and subgroups revealed HTLV-1aD signatures in the envelope, pol, and pX regions. These genomes provide original information that will contribute to further studies on HTLV-1a epidemiology and evolution.
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Estudo de Associação Genômica Ampla , Vírus Linfotrópico T Tipo 1 Humano/genética , Cabo Verde , Humanos , FilogeniaRESUMO
Chikungunya virus (CHIKV) is a mosquito-borne pathogen that emerged in Brazil by late 2014. In the country, two CHIKV foci characterized by the East/Central/South Africa and Asian genotypes, were established in North and Northeast regions. We characterized, by phylogenetic analyses of full and partial genomes, CHIKV from Rio de Janeiro state (2014-2015). These CHIKV strains belong to the Asian genotype, which is the determinant of the current Northern Brazilian focus, even though the genome sequence presents particular single nucleotide variations. This study provides the first genetic characterisation of CHIKV in Rio de Janeiro and highlights the potential impact of human mobility in the spread of an arthropod-borne virus.
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Vírus Chikungunya/genética , Brasil , Febre de Chikungunya/transmissão , Vírus Chikungunya/isolamento & purificação , Genótipo , Humanos , FilogeniaRESUMO
Parvovirus B19 (B19V) infects individuals worldwide and is associated with an ample range of pathologies and clinical manifestations. B19V is classified into three distinct genotypes, all identified in Brazil. Here, we report a complete sequence of a B19V genotype 1A that was obtained by high-throughput metagenomic sequencing. This genome provides information that will contribute to the studies on B19V epidemiology and evolution.
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Genoma Viral/genética , Parvovirus B19 Humano/genética , Brasil , Criança , Evolução Fatal , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Parvovirus B19 Humano/classificação , Análise de Sequência de DNARESUMO
Human T-lymphotropic virus type 1 (HTLV-1) has a global spread, and it is estimated that around 20 million persons are infected. Seven major genetic subtypes are recognized. However, there are complete genomes only from the HTLV-1a (cosmopolitan) and HTLV-1c (Melanesian) subtypes. Here, the first full-length genome of an HTLV-1b strain, a subtype so far restricted to Central African countries, is revealed. The genome size of HTLV-1b SF26, a strain isolated in Brazil, was determined to be 8,267 bp. The genomic analysis showed that all characteristic regions and genes of a prototypic HTLV-1 virus are conserved. This genome can provide information for further studies on the evolutionary history and pathogenic potential of this human oncovirus.
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Genoma Viral , Vírus Linfotrópico T Tipo 1 Humano/genética , África Central , DNA Viral , Bases de Dados Genéticas , Genes Virais , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNARESUMO
The human T cell lymphotropic virus type 1 (HTLV-1), unlike other RNA viruses such as HIV, has a stable genome and has infected humans since remote times. Although the HTLV-1 infection is endemic in South America, there is scarce information about HTLV-1 in Chile and its history of introduction. This study assessed the genomic content of HTLV-1 from Chile and its relationship with HTLV-1 lineages circulating worldwide by phylogenetic reconstruction and dating analyses. A total of 30 HTLV-1 genomes collected from the four continents were used to conduct dating analyses, including the first HTLV-1 genome from Amerindian/Mapuche ethnicity. Estimation was performed using a Bayesian Markov Chain Monte Carlo coalescent-based approach as implemented in the BEAST program. The time of the most recent ancestor of HTLV-1 from Chile was â¼1409 years ago, which coincides with the period of Amerindian population expansion across South America. Our results suggest HTLV-1aA was possibly introduced in Chile during the migrations of the ancestral indigenous populations.
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Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Teorema de Bayes , Chile/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 2 Humano/genética , Humanos , Povos Indígenas , FilogeniaRESUMO
BACKGROUND: Several reports have proposed that the viral load of torque teno virus (TTV) in plasma is a biomarker of immune function in solid organ transplantation (SOT) and in allogeneic hematopoietic stem cell transplantation. Additionally, for the latter one, TTV-DNA quantification in saliva has also been suggested. AIM: to investigate the correlation between the TTV viral load and immune function in paired saliva and plasma samples in patients on kidney transplantation. MATERIALS AND METHODS: TTV-DNA viral load was quantified in paired samples of saliva and plasma from 71 patients before and a short-time after renal-transplantation by real-time PCR. RESULTS: The data obtained from 213 paired samples showed a slight consistency in the comparison between saliva and plasma, with prevalence of TTV-DNA being 58%, 52% and 60% in saliva samples and 60%, 73% and 90% in plasma samples before and at 15-20 and 45-60 days after transplantation, respectively. Additionally, a high TTV viral load was observed in plasma at 15-20 and 45-60 days after transplantation compared to that observed in saliva at the same time. CONCLUSIONS: Overall, monitoring TTV-DNA in saliva samples could be an additional fast non-invasive option to assess the immune functionality in SOT populations.
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Chemoresistance is a significant clinical challenge, limiting the drug response in cancer. Several mechanisms associated with drug resistance have been characterized, and the role of epigenetics in generating resistance to platinum-based drugs has been clarified. Epigenetic mechanisms such as DNA methylation, histone modification, long noncoding RNA, and microRNA affect the expression of genes implicated in absorption, distribution, metabolism and excretion (ADME) of drugs, and other non-ADME genes that encode enzymes involved in the processes of cell proliferation, DNA repair, apoptosis and signal transduction key in the development of chemoresistance in cancer, specifically in platinum-based drugs. This review summarizes current discoveries in epigenetic regulation implicated in platinum drug resistance in cancer and the main clinical trials based on epigenetic therapy, evaluating their potential synergy with platinum-based drugs.
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Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Epigênese Genética/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Compostos de Platina/uso terapêutico , Antineoplásicos/farmacologia , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Humanos , MicroRNAs/genética , Compostos de Platina/farmacologia , RNA Longo não Codificante/genéticaRESUMO
The Epstein-Barr virus (EBV) is a globally dispersed pathogen involved in several human cancers of B-cell and non-B-cell origin. EBV has been classified into EBV-1 and EBV-2, which have differences in their transformative ability. EBV-1 can transform B-cells into LCL more efficiently than EBV-2, and EBV-2 preferentially infects T-cell lymphocytes. The EBNA3A oncoprotein is a transcriptional regulator of virus and host cell genes, and is required in order to transform B-cells. EBNA3A has six peptide motifs called nuclear localization signals (NLSs) that ensure nucleocytoplasmic protein trafficking. The presence of multiple NLSs has been suggested to enhance EBNA3 function or different specificities in different cell types. However, studies about the NLS variability associated with EBV types are scarce. Based on a systematic sequence analysis considering more than a thousand EBNA3A sequences of EBV from different human clinical manifestations and geographic locations, we found differences in NLSs' nucleotide structures among EBV types. Compared with the EBNA3A EBV-1, EBNA3A EBV-2 has two of the six NLSs altered, and these mutations were possibly acquired by recombination. These genetic patterns in the NLSs associated with EBV-1 and EBV-2 provide new information about the traits of EBNA3A in EBV biology.
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Background and Objectives: The aim of this study was to examine the salivary microbiome in healthy peri-implant sites and those with peri-implantitis. Methods: Saliva samples were collected from 21 participants with healthy peri-implant sites and 21 participants with peri-implantitis. The V4 hypervariable region of the 16S rRNA gene was sequenced using the Ion Torrent PGM System (Ion 318™ Chip v2 400). The NGS analysis and composition of the salivary microbiome were determined by taxonomy assignment. Downstream bioinformatic analyses were performed in QIIME (v 1.9.1). Results: Clinical differences according to peri-implant condition status were found. Alpha diversity metrics revealed that the bacterial communities of participants with healthy peri-implant sites tended to have a richer microbial composition than individuals with peri-implantitis. In terms of beta diversity, bleeding on probing (BoP) may influence the microbial diversity. However, no clear partitioning was noted between the salivary microbiome of volunteers with healthy peri-implant sites or volunteers with peri-implantitis. The highest relative abundance of Stenotrophomonas, Enterococcus and Leuconostoc genus, and Faecalibacterium prausnitzii, Haemophilus parainfluenzae, Prevotella copri, Bacteroides vulgatus, and Bacteroides stercoris bacterial species was found in participants with peri-implantitis when compared with those with healthy peri-implant sites. Conclusion: Differences in salivary microbiome composition were observed between patients with healthy peri-implant sites and those with peri-implantitis. BoP could affect the diversity (beta diversity) of the salivary microbiome.
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Microbiota , Peri-Implantite , Estudos de Casos e Controles , Disbiose , Humanos , RNA Ribossômico 16S/genéticaRESUMO
Human T-cell lymphotropic virus type 1 (HTLV-1) is a globally-spread virus. It is estimated that there are about 510 million infected people in the world. HTLV is endemic in Chile, with higher seroprevalence among indigenous people. However, little is known about HTLV-1 genetic diversity, its introduction and dispersion in this country. To gain insights into these issues, a phylogenetic dating analysis was conducted based on Chilean and closed related long terminal repeat sequences. The time tree reconstruction showed that the introduction of HTLV-1aA occurred several times in Chile. It was hypothesized that these introductions took place at least in two different historical moments: (i) during the ancient human migrations and (ii) during/after the European colonization of South America. The present study contributes toward understanding the evolutionary history of HTLV-1 in Chile and South America.
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Infecções por HTLV-I/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Filogenia , Sequências Repetidas Terminais , Chile/epidemiologia , Humanos , Estudos SoroepidemiológicosRESUMO
Gastric cancer (GC) is a significant cancer-related cause of death worldwide. The most used chemotherapeutic regimen in GC is based on platinum drugs such as cisplatin (CDDP). However, CDDP resistance reduces advanced GC survival. In vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize new models of CDDP-resistant GC cell lines (AGS R-CDDP and MKN-28 R-CDDP) obtained through a stepwise increasing drug doses method, in order to understand the molecular mechanisms underlying chemoresistance as well as identify new therapeutic targets for the treatment of GC. Cell viability assays, cell death assays and the expression of resistance molecular markers confirmed that AGS R-CDDP and MKN-28 R-CDDP are reliable CDDP-resistant models. RNA-seq and bioinformatics analyses identified a total of 189 DEGs, including 178 up-regulated genes and 11 down-regulated genes, associated mainly to molecular functions involved in CDDP-resistance. DEGs were enriched in 23 metabolic pathways, among which the most enriched was the inflammation mediated by chemokine and cytokine signaling pathway. Finally, the higher mRNA expression of SERPINA1, BTC and CCL5, three up-regulated DEGs associated to CDDP resistance found by RNA-seq analysis was confirmed. In summary, this study showed that AGS R-CDDP and MKN-28 R-CDDP are reliable models of CDDP resistance because resemble many of resistant phenotype in GC, being also useful to assess potential therapeutic targets for the treatment of gastric cancers resistant to CDDP. In addition, we identified several DEGs associated with molecular functions such as binding, catalytic activity, transcription regulator activity and transporter activity, as well as signaling pathways associated with inflammation process, which could be involved in the development of CDDP resistance in GC. Further studies are necessary to clarify the role of inflammatory processes in GC resistant to CDDP and these models could be useful for these purposes.
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Resistencia a Medicamentos Antineoplásicos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Neoplasias Gástricas/genética , Idoso , Betacelulina/genética , Linhagem Celular Tumoral , Quimiocina CCL5/genética , Cisplatino , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Análise de Sequência de RNA , Neoplasias Gástricas/tratamento farmacológico , alfa 1-Antitripsina/genéticaRESUMO
Colorectal cancer is a heterogeneous disease caused by both genetic and epigenetics factors. Analysing DNA methylation changes occurring during colorectal cancer progression and metastasis formation is crucial for the identification of novel epigenetic markers of patient prognosis. Genome-wide methylation sequencing of paired samples of colon (normal adjacent, primary tumour and lymph node metastasis) showed global hypomethylation and CpG island (CGI) hypermethylation of primary tumours compared to normal. In metastasis we observed high global and non-CGI regions methylation, but lower CGI methylation, compared to primary tumours. Gene ontology analysis showed shared biological processes between hypermethylated CGIs in metastasis and primary tumours. After complementary analysis with The Cancer Genome Atlas (TCGA) cohort, FIGN, HTRA3, BDNF, HCN4 and STAC2 genes were found associated with poor survival. We mapped the methylation landscape of colon normal tissues, primary tumours and lymph node metastasis, being capable of identified methylation changes throughout the genome. Furthermore, we found five genes with potential for methylation biomarkers of poor prognosis in colorectal cancer patients.
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Infecções por HTLV-II/diagnóstico , Hepatite C Crônica/diagnóstico , Vírus Linfotrópico T Tipo 2 Humano/genética , Paraparesia Espástica Tropical/diagnóstico , Brasil , Coinfecção , Genótipo , Infecções por HTLV-II/fisiopatologia , Infecções por HTLV-II/virologia , Hepacivirus/isolamento & purificação , Hepatite C Crônica/fisiopatologia , Hepatite C Crônica/virologia , Vírus Linfotrópico T Tipo 2 Humano/classificação , Vírus Linfotrópico T Tipo 2 Humano/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/fisiopatologia , Paraparesia Espástica Tropical/virologia , FilogeniaRESUMO
The Epstein-Barr virus (EBV) infects more than 90% of the human population, playing a key role in the origin and progression of malignant and non-malignant diseases. Many attempts have been made to classify EBV according to clinical or epidemiological information; however, these classifications show frequent incongruences. For instance, they use a small subset of genes for sorting strains but fail to consider the enormous genomic variability and abundant recombinant regions present in the EBV genome. These could lead to diversity overestimation, alter the tree topology and misinterpret viral types when classified, therefore, a reliable EBV phylogenetic classification is needed to minimize recombination signals. Recombination events occur 2.5-times more often than mutation events, suggesting that recombination has a much stronger impact than mutation in EBV genomic diversity, detected within common ancestral node positions. The Hierarchical Bayesian Analysis of Population Structure (hierBAPS) resulted in the differentiation of 12 EBV populations showed seven monophyletic and five paraphyletic. The populations identified were related to geographic location, of which three populations (EBV-p1/Asia/GC, EBV-p2/Asia II/Tumors and EBV-p4/China/NPC) were related to tumor development. Therefore, we proposed a new consistent and non-simplistic EBV classification, beneficial in minimizing the recombination signal in the phylogeny reconstruction, investigating geography relationship and even infer associations to human diseases. These EBV classifications could also be useful in developing diagnostic applications or defining which strains need epidemiological surveillance.
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Infecções por Vírus Epstein-Barr/virologia , Genômica/métodos , Herpesvirus Humano 4/classificação , Recombinação Genética , Ásia , Teorema de Bayes , China , Monitoramento Epidemiológico , Variação Genética , Genoma Viral , Herpesvirus Humano 4/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Filogenia , Filogeografia , Sequenciamento Completo do GenomaRESUMO
INTRODUCCIÓN: El virus del papiloma humano de alto riesgo (VPH-AR) es responsable del cáncer de cuello uterino y sus lesiones preneoplásicas. Los genotipos VPH16 y VPH18 son los más frecuentes en este cáncer. La integración del VPH-AR en el genoma de la célula hospedera es crucial en la carcinogénesis cervical, pero la etapa en que ocurre en la población chilena es incierta. OBJETIVO: Evaluar la integración de VPH16 y VPH18 en lesiones pre-neoplásicas de cuello uterino. MÉTODOS: Se analizaron 108 muestras de raspados cervicales. El VPH se genotipificó mediante reacción de polimerasa en cadena (RPC) e hibridación no radiactiva. La integración de VPH16 y VPH18 se determinó por presencia del gen E2 mediante RPC. RESULTADOS: VPH16 y VPH18 se detectaron en 36,1% y 12,0% de las muestras, respectivamente. El VPH16 se integró en 23,1% de los casos de VPH16, mientras que VPH18 se integró en 100% de las muestras positivas para este genotipo. CONCLUSIONES: La integración VPH-AR es un evento temprano en la carcinogénesis cervical que ocurre en casi la mitad de las lesiones pre-neoplásicas y es más frecuente en VPH18 que en VPH16. La evaluación de la integración VPH-AR puede ser una herramienta útil para detectar el virus en la población chilena.
BACKGROUND: High-risk Human Papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer and its preneoplastic lesions. HPV16 and 18 are the most frequent HR-HPV genotypes detected in cervical cancer. HR-HPV genome integration into the host cell is an important event in the carcinogenic process. However, it remains uncertain which stage of cervical carcinogenesis HPV16 and 18 integration occurs in the Chilean population. AIM: The goal of this study was to evaluate HPV16 and HPV18 integration in preneoplastic lesions of the cervix. METHODS: DNA was extracted from 108 cervical scrape samples with preneoplastic lesions. HPV was genotyped using PCR and non-radioactive hybridization. The integration status of HPV16 and HPV 18 was determined by evaluating the E2 gene presence through PCR. RESULTS: HPV16 and HPV18 tested positive in 36.1% and 12.0% of samples, respectively. HPV16 was found integrated in 23.1% of HPV 16 cases, while HPV 18 in 100% of samples positive for this viral genotype. CONCLUSIONS: HR-HPV integration is an early event in cervical carcinogenesis, occurring in nearly half of preneoplastic lesions and being more frequent in HPV18 than in HPV16. The evaluation of HR-HPV integration can be utilized as a complementary tool for detecting HPV in the Chilean population.