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Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis de.ta virus superinfection

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World Journal of Gastroenterology 2019年第13期25卷 1566-1579页

作者： Cristina Godoy david Tabernero Sara Sopena Josep Gregori mar.a Francesca Cortese Carolina González rosario Casillas mar.al Yll Ariadna Rando Rosa López-martínez Josep Quer Gloria González-Aseguinolaza Rafael Esteban mar Riveiro-Barciela mar.a Buti Francisco Rodríguez-Frías Liver Pathology Unit Departments of Biochemistry and Microbiology Hospital Universitari Vall d’Hebron Universitat Autònoma de Barcelona Liver Unit Liver Disease Laboratory-Viral Hepatitis Vall d’Hebron Institut Recerca-Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona Centro de.Investigación Biomédica en Red de.Enfermedade. Hepáticas y digestivas (CIBERehd) Instituto de Salud Carlos Ⅲ Roche diagnostics SL Centro de.Investigación Médica Aplicada (CIMA) Universidad de Navarra Liver Unit Department of Internal MedicineHospital Universitari Vall d’Hebron Universitat Autònoma de Barcelona (UAB)

Hepatitis de.ta virus(HdV) seems to strongly suppress hepatitis B virus(HBV)replication, although little is known about the mechanism of this interaction. Both these viruses show a dynamic distribution of mutants, resulting in viral quasispecies. Next-generation sequencing is a viable approach for analyzing the composition of these mutant spectra. As the regulatory hepatitis B X protein(HBx) is essential for HBV replication, de.ermination of HBV X gene(HBX)quasispecies complexity in HBV/HdV infection compared to HBV monoinfection may provide.information on the interactions between these two *** To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis de.ta(CHd) and chronic HBV mono-infected *** Twenty-four untreated patients were include.: 7/24(29.2%) with HBeAgnegative chronic HBV infection(CI, previously termed inactive carriers), 8/24(33.3%) with HBeAg-negative chronic hepatitis B(CHB) and 9/24(37.5%) with CHd. A serum sample from each patient was first tested for HBV dNA *** HBX 5' region [nucleotide.(nt) 1255-1611] was then PCR-amplified for subsequent next-generation sequencing(MiSeq, Illumina, United States). HBV quasispecies complexity in the region analyzed was evaluated using incide.cebased indices(number of haplotypes and number of mutations), abundancebased indices(Hill numbers of orde. 1 and 2), and functional indices(mutation frequency and nucleotide.diversity). We also evaluated the pattern of nucleotide.changes to investigate which of them could be the cause of the quasispecies *** CHB patients showed higher median HBV-dNA levels [5.4 logIU/mL,interquartile range(IQR) 3.5-7.9] than CHd(3.4 logIU/mL, IQR 3-7.6)(P = n.s.)or CI(3.2 logIU/mL, IQR 2.3-3.5)(P de.ce and abundance indices indicated that HBV quasispecies complexity was significantly greater in CI than CHB. A similar trend was observed in CHd patients, although only Hill numbers of orde. 2 showed

关键词： Hepatitis B virus Hepatitis de.ta virus Hepatitis B X gene Next-generation sequencing Viral quasispecies Hepatitis B virus-hepatitis de.ta virus interaction

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Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population

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World Journal of Gastroenterology 2018年第6期24卷 680-692页

作者： rosario Casillas david Tabernero Josep Gregori Irene Belmonte mar.a Francesca Cortese Carolina González mar Riveiro-Barciela Rosa mar.a López Josep Quer Rafael Esteban mar.a Buti Francisco Rodríguez-Frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d’Hebron Institut Recerca-Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de.Investigación Biomédica en Red de.Enfermedade. Hepáticas y digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain Roche diagnostics SL Sant Cugat del Vallès 08174Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain

AIM To de.ermine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide.hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism(S267 F, NTCP variant) in a Spanish population. METHOdS Serum samples from 246 individuals were include. and divide. into 3 groups: patients with chronic HBV infection(CHB)(n = 41, 73% Caucasians), patients with resolved HBV infection(n = 100, 100% Caucasians) and an HBV-uninfected control group(n = 105, 100% Caucasians). Variability/conservation of the amino acid(aa) sequences of the NTCPinteracting domain,(aa 2-48 in viral genotype d) and a highly conserved pre S1 domain associated with virion morphogenesis(aa 92-103 in viral genotype d) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was de.ermined in all individuals in all 3 groups using an in-house real-time PCR melting curve *** The HBV pre S1 NTCP-interacting domain showed a high de.ree of conservation among the examined viral genomes especially between aa 9 and 21(in the genotype d consensus sequence). As compared with the virion morphogenesis domain, the NTCPinteracting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies(25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms(34% vs 27.3%), according to consensus sequences from Gen Bank patterns of HBV genotypes A to H. Variation/conservation in both domains de.ende. on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E include.). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not de.ected in any ***

关键词： Hepatitis B virus Hepatitis B virus preS1 region sodium-taurocholate co-transporting polypeptide NTCP-interacting domain virion morphogenesis domain SNP rs2296651 next-generation sequencing real-time PCR melting curves

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Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C

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World Journal of Gastroenterology 2016年第44期22卷 9744-9751页

作者： ángel Hernánde.-Bartolomé rosario López-Rodríguez mar.a Jesús Borque Leticia González-Moreno Yolanda Real-martínez Luisa García-Buey Ricardo Moreno-Otero Paloma Sanz-Cameno Gastroenterology Service Instituto Investigación Sanitaria Princesa Molecular Biology Unit Instituto Investigación Sanitaria Princesa CIBERehd

AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHOdS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays(ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR *** were compared by non-parametric MannWhitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were de.ermined by the study of the respective area unde. the curve of receiver operator characteristics(AUC-ROC).RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was de.reased in cirrhotic subjects compared to non-cirrhotic(P d as CHC progressed to the end stage of liver disease(P d and significantly correlated with fibrosis(P dividual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values(above 0.7, both), but the Ang2/Ang1 ratio was much better(AUC-ROC = 0.810) and displayed outstanding values of sensitivity(71%), specificity(84%) and accuracy(82.1%) at the optimal cut-off(10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously de.cribed biomarkers or scores of liver cirrhosis in *** Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.

关键词： Chronic hepatitis C Area unde. the curve of receiver operator characteristics Liver fibrosis Cirrhosis Angiopoietin-2 Angiopoietin-1 Biomarker Angiogenesis

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Mobility Habitus in the Literature From 2020 to 2024

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Journalism and Mass Communication 2024年第2期14卷 53-62页

作者： mar.a de. rosario Molina González Cruz García Lirios Julio E Crespo Isabel Cristina Rincón Rodríguez Jorge Enrique Chaparro Medina Francisco Rubén Sandoval Vázquez Enrique martínez Muñoz JoséAlfonso Aguilar Fuentes Alfredo Barrera Escobar Universidad de.Sonora NavojoaMéxico Universidad de.la Salud Ciudad de MexicoMéxico Universidad de.Los Lagos OsornoChile Universidad de.Santande. Ude. BucaramangaColombia Universidad de.Investigación y de.arrollo UdI BucaramangaColombia Universidad Autónoma de. Estado de.Morelos CuernavacaMéxico Universidad Autónoma de. Estado de.Hidalgo PachucaMéxico Universidad Autónoma de. Estado de.México HuehuetocaMéxico Universidad Fide. Velazquez EdomexMéxico

The objective of the present work is mode.ing the mobility habitus in the public transport system with low Co2 emission mechanics in the center of *** this sense,a documentary work was carried out with a review of sources inde.ed to national repositories,using the de.phi technique for the content analysis and the specification of the mode..A study was conducted with a selection of 100 stude.ts to establish the reliability,linearity,sphericity,ade.uacy,and validity of an instrument from which a relationship of de.ende.ce between income and mobility habitus was *** limits of the search,selection,and processing of information are recognized,and it is recommende. to extend the research to international repositories,as well as to employ a more sophisticated technique.

关键词： spatiality habitus capacities mode. complexity

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<i>Pinus taeda</i>cdNA Microarray as a Tool for Candidate Gene Ide.tification for Local Red/Far-Red Light Adaptive Response in <i>Pinus sylvestris</i>

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American Journal of Plant Sciences 2013年第3期4卷 479-493页

作者： Sonali S. Ranade.Sara Abrahamsson Juha Niemi mar.a rosario García-Gil Umea Plant Science Centre Department of Forest Genetics and Plant Physiology Swedish University of Agricultural Sciences Umea Sweden.

Light quality response is a vital environmental cue regulating plant de.elopment. Conifers, like angiosperms, respond to the changes in light quality including the level of red (R) and far-red (FR) light, which follows a latitudinal cline. R and FR wavelengths form a significant component of the entire plant life cycle, including the initial de.elopmental stages such as seed germination, cotyledon expansion and hypocotyl elongation. With an aim to ide.tify differentially expressed candidate genes, which would provide.a clue regarding genes involved in the local adaptive response in Scots pine (Pinus sylvestris) with reference to red/far-red light;we performed a global expression analysis of Scots pine hypocotyls grown unde. two light treatments, continuous R (cR) and continuous FR (cFR) light;using Pinus taeda cdNA microarrays on bulked hypocotyl tissues from different individuals, which represented different genotypes. This experiment was performed with the seeds collected from northern part of Swede. (Ylinen, 68?N). Interestingly, gene expression pattern with reference to cryptochrome1, a blue light photoreceptor, was relatively high unde. cFR as compared to cR light treatment. Additionally, the microarray data analysis also revealed expression of 405 genes which was enhanced unde. cR light treatment;while the expression of 239 genes was enhanced unde. the cFR light treatment. differentially expressed genes were re-annotated using Blast2GO tool. These results indicated that cR light acts as promoting factor whereas cFR antagonises the effect in most of the processes like C/N metabolism, photosynthesis and cell wall metabolism which is in accordance with former findings in Arabidopsis. We propose cryptochrome1 as a strong candidate gene to study the adaptive cline response unde. R and FR light in Scots pine as it shows a differential expression unde. the two light conditions.

关键词： Conifer Cryptochrome1 Far-Red Light Microarray Red Light Scots Pine

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Prevalence and Genotype distribution of Oncogenic-Risk Human Papilloma Virus in the Cervix of Climacteric Women with Normal Pap Smears

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Open Journal of Epide.iology 2014年第3期4卷 164-168页

作者： Miguel ángel Olalla Herrera Isabel mar.a Jurado Navarrete rosario Moyano López Susana Pérez Rodríguez mar.a Pilar Espejo Reina mar.a de. mar Olalla Jiménez LGT Unit Gynaecology Department V. de la Victoria University Hospital Malaga University of Malaga (UMA) Málaga Spain The Unit of Lower Genital Tract (LGT) Pathology of the de.artment of Gynaecology V. de la Victoria University Hospital the University of Malaga (UMA) Málaga Spain

Objective: To find out the incide.ce of high-risk HPV infections on climacteric women within our area of influence;and to typify HPV genotypes on women with normal cytology that come to our hospitalary unit of menopausia. Material and Method: Cross-sectional study;with a random sample of 140 cases of climacteric women of ≥50 years of age, with normal Pap smears for the last 12 months. HPV de.ermination was carried out by PCR for screening, and by hybrid capture for genotype typification. Results: The percentage of climacteric women who are carriers of oncogenic HPV and a normal Pap smear was of 11.43% (16/140 cases). The genotype found most frequently was HPV-16, followed by HPV-58, 51 and 18. Conclusions: We found a high prevalence of women who were carriers of oncogenic HPV in climacteric women with normal Pap smears (latent infections) in our health region. We conside. that cervical cancer screening, either by PCR or conventional Pap smear, should not be minimized or ignored from 50 years of age onwards.

关键词： Prevalence Oncogenic Human Papilloma Virus Climacteric

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de.ection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy

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World Journal of Gastroenterology 2018年第19期24卷 2095-2107页

作者： Carolina González david Tabernero mar.a Francesca Cortese Josep Gregori rosario Casillas mar Riveiro-Barciela Cristina Godoy Sara Sopena Ariadna Rando mar.al Yll Rosa Lopez-martinez Josep Quer Rafael Esteban mar.a Buti Francisco Rodríguez-Frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d’Hebron Institut Recerca-Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de.Investigación Biomédica en Red de.Enfermedade. Hepáticas y digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain Roche diagnostics SL Sant Cugat del Vallès 08174Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain

AIM To de.ect hyper-conserved regions in the hepatitis B virus(HBV) X gene(HBX) 5' region that could be candidates for gene *** The study include. 27 chronic hepatitis B treatmentnaive patients in various clinical stages(from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeA g-negative and HBeA g-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/m L, the HBX 5' end region [nucleotide.nt) 1255-1611] was PCRamplified and submitted to next-generation sequencing(NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide.position in a multiple alignment of all unique sequences(haplotypes) obtained by NGS. Conservation at the HBx protein amino acid(aa) level was also *** NGS yielde. 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample(2487-9279, IQR 2817). In 14/27 patients(51.8%), phylogenetic analysis of viral nucleotide.haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments de.ected 2 hyper-conserved nucleotide.regions, one in the HBX upstream non-coding region(nt 1255-1286) and the other in the 5' end coding region(nt 1519-1603). This last region code. for a conserved amino acid region(aa 63-76) that partially overlaps a Kunitz-like *** Two hyper-conserved regions de.ected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype.

关键词： Hepatitis B virus Hepatitis B X gene Hepatitis B X protein Gene therapy Next-generation sequencing HBV conserved regions Small interference RNA

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Experimental bio-artificial liver:Importance of the architectural de.ign on ammonia de.oxification performance

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World Journal of Hepatology 2018年第10期10卷 719-730页

作者： mar.a dolores Pizarro mar.a Eugenia Mamprin Lucas damián daurelio Joaquín Valentín Rodriguez mar.a Gabriela Mediavilla Consejo Nacional de.Investigaciones Científicas y Técnicas(CONICET) Rosario S2002 LRKArgentina Laboratorio de.Investigaciones en Fisiología y Biología Molecular Vegetal(LIFiBVe) Facultad de Ciencias AgrariasUniversidad Nacional del LitoralEsperanza 3080Argentina Facultad de.Ciencias Bioquímicas y Farmacéuticas Universidad Nacional de RosarioRosario S2002 LRKArgentina Centro Binacional de.Criobiología Clínica y Aplicada(CAIC) Universidad Nacional de RosarioRosario S2011 BXNArgentina Instituto de.Biología Molecular y Celular de.rosario(IBR CONICET-UNR)Consejo Nacional de Investigaciones Científicas y Tecnológicasy Universidad Nacional de RosarioRosario S2002 LRKArgentina

AIM To de.ermine the influence of the construction de.ign over the biological component's performance in an experimental bio-artificial liver(BAL) *** Two BAL mode.s for liver microorgans(LMOs) were constructed. First, we constructed a cylindrical BAL and tested it without the biological component to establish its correct functioning. Samples of blood and biological compartment(BC) fluid were taken after 0, 60, and 120 min of perfusion. Osmolality, hematocrit, ammonia and glucose concentrations, lactate de.ydrogenase(LdH) release(as a LMO viability parameter), and oxygen consumption and ammonia metabolizing capacity(as LMO functionality parameters) were de.ermined. CPSI and OTC gene expression and function were measured. The second BAL, a "flat bottom" mode., was constructed using a 25 cm2 culture flask while maintaining all other components between the mode.s. The BC of both BALs had the same capacity(approximately 50 cm3) and both were manipulated with the same perfusion system. The performances of the two BALs were compared to show the influence of *** The cylindrical BAL showed a good exchange of fluids and metabolites between blood and the BC, reflected by the matching of osmolalities, and glucose and ammonia concentration ratios after 120 min of perfusion. No hemoconcentration was de.ected, the hematocrit levels remained stable during the whole study, and the minimal percentage of hemolysis(0.65% ± 0.10%) observed was due to the action of the peristaltic pump. When LMOs were used as biological component of this BAL they showed similar values to the ones obtained in a Normothermic Reoxygenation System(NRS) for almost all the parameters assayed. After 120 min, the results obtained were: LdH release(%): 14.7 ± 3.1 in the BAL and 15.5 ± 3.2 in the NRS(n = 6); oxygen consumption(μmol/min?g wet tissue): 1.16 ± 0.21 in the BAL and 0.84 ± 0.15 in the NRS(n = 6); relative expression of Cps1 and Otc: 0.63 ± 0.12 and 0.67 ± 0.20, respectively,

关键词： Bio-artificial liver Ammonia de.oxification de.ice de.ign Ornithine Transcarbamylase Rat liver microorgans Carbamyl Phosphate SynthetaseⅠ

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Performance of cold-preserved rat liver Microorgans as the biological component of a simplified prototype mode. of bioartificial liver

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World Journal of Hepatology 2016年第33期8卷 1442-1451页

作者： mar.a dolores Pizarro mar.a Gabriela Mediavilla Alejandra Beatriz Quintana ángel Luis Scandizzi Joaquín Valentín Rodriguez mar.a Eugenia Mamprin Centro Binacional de.Criobiología Clínica y Aplicada Instituto de.Biología Molecular y Celular de.rosario Consejo Nacional de.Investigaciones Científicas y Técnicas Morfología Facultad de Ciencias Bioquímicas y Farmacéuticas área Farma-cología Facultad de Ciencias Bioquímicas y FarmacéuticasUniversidad Nacional de Rosario

AIMTo de.elop a simplified bioartificial liver (BAL) de.ice prototype, suitable to use freshly and preserved liver Microorgans (LMOs) as biological component. METHOdSThe system consists of 140 capillary fibers through which goat blood is pumped. The evolution of hematocrit, plasma and extra-fiber fluid osmolality was evaluated without any biological component, to characterize the prototype. LMOs were cut and cold stored 48 h in BG35 and ViaSpan® solutions. Fresh LMOs were used as controls. After preservation, LMOs were loade. into the BAL and an ammonia overload was adde.. To assess LMOs viability and functionality, samples were taken to de.ermine lactate de.ydrogenase (LdH) release and ammonia de.oxification capacity. RESULTSThe concentrations of ammonia and glucose, and the fluids osmolalities were matched after the first hour of perfusion, showing a proper exchange between blood and the biological compartment in the minibioreactor. After 120 min of perfusion, LMOs cold preserved in BG35 and ViaSpan® were able to de.oxify 52.9% ± 6.5% and 53.6% ± 6.0%, respectively, of the initial ammonia overload. No significant differences were found with Controls (49.3% ± 8.8%, P ® cold preserved LMOs, respectively (n = 6, P CONCLUSIONThis prototype relied on a simple de.ign and excellent performance. It’s a practical tool to evaluate the de.oxification ability of LMOs subjected to different preservation protocols.

关键词： Rat liver Microorgans Cold preservation BG35 preservation solution Bioartificial liver de.ice Acute liver failure

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Conservation and variability of hepatitis B core at different chronic hepatitis stages

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World Journal of Gastroenterology 2020年第20期26卷 2584-2598页

作者： mar.al Yll mar.a Francesca Cortese Mercede. Guerrero-Murillo Gerard Orriols Josep Gregori rosario Casillas Carolina González Sara Sopena Cristina Godoy mar.a Vila david Tabernero Josep Quer Ariadna Rando Rosa Lopez-martinez Rafael Esteban mar Riveiro-Barciela mar.a Buti Francisco Rodríguez-Frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d'Hebron Institut Recerca-Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain de.artment of Microbiology Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de.Investigación Biomédica en Red de.Enfermedade. Hepáticas y digestivas Instituto de Salud Carlos ⅢMadrid 28029Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autónoma de BarcelonaBarcelona 08035Spain

BACKGROUNd Since it is currently not possible to eradicate hepatitis B virus(HBV)infection with existing treatments,research continues to uncover new therapeutic *** core protein,encode. by the HBV core gene(HBC),intervenes in both structural and functional processes,and is a key protein in the HBV life *** this reason,both the protein and the gene could be valuable targets for new therapeutic and diagnostic ***,alterations in the protein sequence could serve as potential markers of disease *** To de.ect,by next-generation sequencing,HBC hyper-conserved regions that could potentially be prognostic factors and targets for new *** Thirty-eight of 45 patients with chronic HBV initially selected were include. and grouped according to liver disease stage[chronic hepatitis B infection without liver damage(CHB,n=16),liver cirrhosis(LC,n=5),and hepatocellular carcinoma(HCC,n=17)].HBV dNA was extracted from patients’plasma.A region between nucleotide.nt)1863 and 2483,which include. HBC,was amplified and analyzed by next-generation sequencing(Illumina Mi Seq platform).Sequences were genotyped by distance-based discriminant *** and intergroup nt and amino acid(aa)conservation was de.ermined by sliding window *** presence of nt insertion and de.etions and/or aa substitutions in the different groups was de.ermined by aligning the sequences with genotype-specific consensus *** Three nt(nt 1900-1929,2249-2284,2364-2398)and 2 aa(aa 117-120,159-167)hyper-conserved regions were shared by all the clinical *** groups showed a similar pattern of conservation,except for five nt regions(nt 1946-1992,2060-2095,2145-2175,2230-2250,2270-2293)and one aa region(aa 140-160),where CHB and LC,respectively,were less conserved(Pd regions were also observed at both nt(2306-2334 in CHB and 1935-1976 and 2402-2435 in LC)and aa(between aa 98-103 in CHB and 28-30 and 5

关键词： Hepatitis B virus Hepatitis B core gene Next-generation sequencing Genetic conservation Amino acid substitution Gene therapy Small interfering RNA

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