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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 | Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy显示文摘AIM To detect hyper-conserved regions in the hepatitis B virus(HBV) X gene(HBX) 5' region that could be candidates for gene therapy.METHODS The study included 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 analyzed.RESULTS NGS yielded 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 detected 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 coded for a conserved amino acid region(aa 63-76) that partially overlaps a Kunitz-like domain.CONCLUSION Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype. | Carolina González David Tabernero Maria Francesca Cortese Josep Gregori Rosario Casillas Mar Riveiro-Barciela Cristina Godoy Sara Sopena Ariadna Rando Marcal Yll Rosa Lopez-Martinez Josep Quer Rafael Esteban Maria Buti Francisco Rodríguez-Frías | 2018 | World Journal of Gastroenterology2018，24，19： | 6 |
| 3 | Malignant melanoma of soft parts (clear cell sarcoma): a study of 17 cases, with emphasis on prognostic factors显示文摘 | Sara AS Evans HL Benjamin RS | 1990 | Cancer1990，65，： | 1 |
| 4 | The behavior and emotional correlates of epilepsy in adolescence : a 7 - year follow - up study 显示文摘 | David AS Sara ER Robert CP | 2002 | Epilepsy &Behavior2002，3，： | 1 |
| 5 | Vanilloid re- ceptor agonists and antagonists are mitochondrial inhibitors: How vanilloids cause nonvanilloid re- ceptor mediated cell death 显示文摘 | Andriani A Paul AS Sara V | 2007 | Biochem Biophys Res Commun2007，354，1： | 1 |
| 6 | Estrogen activates matrix metallopro-teinases-2 and-9 to increase beta amyloid degradation显示文摘 | Sara M Maria AS | 2012 | Mol Cell Neurosci2012，49，： | 1 |
| 7 | Giant cell tumor of bone a clinic pathological and DNA flow cytometric analysis显示文摘 | Sara AS Ayaia AG EI-Naggar A | 1990 | Cancer1990，66，10： | 1 |
| 8 | The behavior and emotional correlates of epilepsy in adolescence: a 7 - year follow - up study 显示文摘 | David AS Sara ER Robert CP | 2002 | Epilepsy Behav2002，3，： | 1 |
| 9 | MR imaging of extracranial nerve sheath tumors显示文摘 | Varma DG Moulopoulos A Sara AS | 1992 | J Comput Assist Tomogr1992，16，： | 1 |
| 10 | Sperm mRNA Transcripts Are Indicators of Sub-Chronic Low Dose Testicular Injury in the Fischer 344 Rat显示文摘 | Sara EP Linnea MA Moses AS | 2012 | PLoS One2012，7，44： | 1 |
| 11 | Malignant melanoma of soft parts (clear cell sarcoma):a study of 17 cases,with emphasis on prognostic factors显示文摘 | Sara AS Evans HL Benjamin RS | 1990 | Cancer1990，65，2： | 1 |
| 12 | The behavior and emotional correlates of epilepsy in adolescence :a 7-year follow-up study 显示文摘 | David AS Sara ER Robert CP | 2002 | E)ilepsv Behav2002，3，4： | 1 |
| 13 | The behavior and emotional correlates of epilepsy in adolescence: a 7 year follow-up study 显示文摘 | David AS Sara ER Robert CP | 2002 | Epilepsy Behavior2002，3，4： | 1 |
| 14 | MR imaging of extraeranial nerve sheath tumors显示文摘 | Varma DG Moulopoulos A Sara AS | 1992 | J Comput Assist Tomogr1992，16，3： | 1 |
| 15 | The behavior and emotional correlates of epilepsy in adolescence : a 72 - year follow up study 显示文摘 | David AS Sara ER Robert CP | 2002 | Epilepsy&Behavior2002，3，： | 1 |
| 16 | The behavior and emotional correlates of epilepsy in adolescence: a 7 - year follow - up study显示文摘 | David AS Sara ER Robert GP | 2002 | Epilepsy Behav2002，3，： | 1 |
| 17 | Malignant melanoma of soft parts(clear cell sarcoma):A study of 17cases with emphasis on prognostic factors显示文摘 | Evans HL Benjamin RS | 1990 | Cancer1990，65，2： | 1 |
| 18 | Malignant melanoma of soft parts clear cell sarcoma:A study of 17 cases with emphasis on prognostic factors显示文摘 | Sara AS Evans HL Benjamin RS | | 0，，02： | 1 |
| 19 | MR imaging of extracranial nerve sheath tumors 显示文摘 | Varma DG Moulopoulos A Sara AS | 1992 | Comput Assist Tomogr1992，16，： | 1 |
| 20 | MR imaging of extracranial nerve sheath tumors显示文摘 | Varma DG Moulopoulos A Sara AS | 1992 | J Compui Assist Tomogr1992，16，： | 1 |
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