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| 1 | Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection显示文摘Hepatitis delta 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, determination of HBV X gene(HBX)quasispecies complexity in HBV/HDV infection compared to HBV monoinfection may provide information on the interactions between these two viruses.AIM To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta(CHD) and chronic HBV mono-infected patients.METHODS Twenty-four untreated patients were included: 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 levels.The HBX 5' region [nucleotides(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 incidencebased indices(number of haplotypes and number of mutations), abundancebased indices(Hill numbers of order 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 complexity.RESULTS 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 < 0.01) patients. The incidence 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 order 2 showed statistically significant differences(CHB2.81, IQR 1.11-4.57 vs CHD 8.87, 6.56-11.18, P = 0.038). There were no significant differences in the functional indices, but CI and CHD patients also showed a trend towards greater complexity than CHB. No differences were found for any HBV quasispecies complexity indices between CHD and CI patients. G-to-A and C-to-T nucleotide changes, characteristic of APOBEC3 G, were higher in CHD and CI than in CHB in genotype A haplotypes, but not in genotype D. The proportion of nt G-to-A vs A-to-G changes and C-to-T vs T-to-C changes in genotype A and D haplotypes in CHD patients showed no significant differences. In CHB and CI the results of these comparisons were dependent on HBV genotype.CONCLUSION The lower-replication CHD and CI groups show a trend to higher quasispecies complexity than the higher-replication CHB group. The mechanisms associated with this greater complexity require elucidation. | Cristina Godoy David Tabernero Sara Sopena Josep Gregori Maria Francesca Cortese Carolina González Rosario Casillas Mar?al Yll Ariadna Rando Rosa López-Martínez Josep Quer Gloria González-Aseguinolaza Rafael Esteban Mar Riveiro-Barciela Maria Buti Francisco Rodríguez-Frías | 2019 | World Journal of Gastroenterology2019，25，13： | 6 |
| 2 | Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population显示文摘AIM To determine 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 included and divided 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 determined in all individuals in all 3 groups using an in-house real-time PCR melting curve analysis.RESULTS The HBV pre S1 NTCP-interacting domain showed a high degree 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 depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E included). 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 detected in any participant.CONCLUSION In our CHB population, the NTCP-interacting domain was highly conserved, particularly the proline residues and essential amino acids related with the NTCP interaction, and the prevalence of rs2296651 was low/null. | Rosario Casillas David Tabernero Josep Gregori Irene Belmonte Maria Francesca Cortese Carolina González Mar Riveiro-Barciela Rosa Maria López Josep Quer Rafael Esteban Maria Buti Francisco Rodríguez-Frías | 2018 | World Journal of Gastroenterology2018，24，6： | 5 |
| 3 | Mechanochemical synthesis of hercynite显示文摘 | Pablo M. Botta Esteban F. Aglietti José M. Porto López | 2002 | Materials Chemistry and Physics2002，，1： | 2 |
| 4 | Conventional and molecular diagnostic strateg/es for prosthetic joint infections 显示文摘 | Esteban J Sorli L Alentorn-Geli E | 2014 | Expert Rev Mol Diagn2014，14，1： | 1 |
| 5 | Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal - cell carcinoma treated with first - line sunitinib : a muhicentre, observational, prospective study 显示文摘 | GARCIA - DONAS J ESTEBAN E LEANDRO - GARCIA L J | 2011 | Lancet Oncol2011，12，12： | 1 |
| 6 | Biocatalysis : towards ever greener biodiesel production 显示文摘 | ROBLES - MEDINA A GONZ:LEZ - MORENO P A ESTEBAN - CERDAN L | 2009 | Biotechnol Adv2009，27，4： | 1 |
| 7 | Production of triacylglycerols rich in palmitic acid at position 2 as intermediates for the synthesis of human milk fat substitutes by enzymatic acidolysis显示文摘 | JIM(E)NEZ M J ESTEBAN L ROBLES A | | 0，，： | 1 |
| 8 | Hepatitis B vaccination in liver transplant candidates显示文摘 | Castells L Esteban R | 2001 | Eur J Gastroenterol Hepatol2001，13，4： | 1 |
| 9 | Effects of continuous activation of vitamin D and Wnt response pathways on osteoblastic proliferation and differentiation 显示文摘 | SHI YC WORTON L ESTEBAN L | 2007 | Bone2007，41，1： | 1 |
| 10 | Synthesis of structured lipids by two enzymatic steps:ethanolysis of fish oils and esterification of 2-monoacylglycerols显示文摘 | MU(N)(I)O M M ROBLES A ESTEBAN L | | 0，，： | 1 |
| 11 | Hepatitis C virus antibodies among risk groups in Spain显示文摘 | Esteban J L Esteban R Viladomiu L | 1989 | Lancet1989，2，8658： | 1 |
| 12 | The bone marrow-derived human mesenchymal stem cel:potential progenitor of the endometrial stromal fibroblast显示文摘 | Aghajanova L Horcajadas JA Esteban FJ | | 0，，06： | 1 |
| 13 | Production of triacylglycerols rich in palmitic acid at sn-2 position by lipase- catalyzed acidolysis显示文摘 | Jimenez M J Esteban L Robles A | 2010 | Biochemical Engineering Journal2010，51，3： | 1 |
| 14 | Enzymatic production of human milk fat substitutes containing palmitic and docosahexaenoic acids at Sn-2 position and oleic acid at Sn-1,3 positions显示文摘 | ROBLES A JIM(E)NEZ M J ESTEBAN L | | 0，，： | 1 |
| 15 | Lipid extraction from the microalga Phaeodactylum tricornutum 显示文摘 | RAMIREZ F A ESTEBAN C L ROBLES M A | 2007 | Eur J Lipid Sci Technol2007，109，2： | 1 |
| 16 | The bone marrow-derived human mesenchymal stem cel:potential progenitor of the endometrial stromal fibroblast显示文摘 | Aghajanova L Horcajadas JA Esteban FJ | | 0，，06： | 1 |
| 17 | Hydrogen production from glycerol on Ni/Al 2 O 3 cata-lyst显示文摘 | Sánchez Esteban A D’Angelo Miguel A Comelli Raúl A | 2010 | International Journal of Hydrogen Energy2010，35，： | 1 |
| 18 | Wright, Urban Structure and Growth 显示文摘 | Esteban R H Mark L J | 2007 | Review of Economic Studies2007，74，2： | 1 |
| 19 | The bone marrow-de- rived human mesenchymal stem cell: potential progenitor of the endometrial stromal fibroblast显示文摘 | Aghajanova L Horcajadas J A Esteban F J | 2010 | Biot Reprod2010，2，6： | 1 |
| 20 | Informative advertising and optimal targeting in a monopoly显示文摘 | Esteban L Gil A Hemandez J M | 2001 | The Journal oflndustrial Economics2001，49，2： | 1 |
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