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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 | NFkappaB and AP-1 mediate transcriptional responses to oxidative stress in skeletal muscle cells显示文摘 | ZHOU L Z H JOHNSON A P RANDO T A | 2001 | Free Radical Biology and Medicine2001，31，11： | 1 |
| 3 | An allele associated with a non detectable amount of αs2-casein in goat milk 显示文摘 | Ramunno L Pappalardo M Rando A | 2001 | Anim Genet2001，32，： | 1 |
| 4 | Technology insight:therapy for Duehenne muscular dystrophy-an opportunity for personalized medicine?显示文摘 | LIM L E RANDO T A | 2008 | Nat Clin Pract Neuml2008，4，3： | 1 |
| 5 | Emerging models and paradigms for stem cell ageing显示文摘 | Jones D L Rando T A | 2011 | Nat Cell Biol2011，13，5： | 1 |
| 6 | Statistical study of the influence of fungicide treatments (mancozeb, zoxamide and copper oxychloride) on heavy metal concentrations in Sicilian red wine显示文摘 | LA PERA L DUGO G RANDO R | 2008 | Food Addit Contam2008，3，25： | 1 |
| 7 | A review on large deploy able structures for astrophysics missions显示文摘 | Puig L Barton A Rando N | 2010 | Acta Astro- nautica2010，67，12： | 1 |
| 8 | A review on large deployablestructures for astrophysics missions 显示文摘 | Puig L Barton A Rando N | 2010 | Acta Astronautica2010，67，： | 1 |
| 9 | Flexible uretemrenoscopy(URS) : technique and results显示文摘 | Cansino Alcaide JR Reinoso Elbers J Lopez Sanchez D Perez Gonzalez S Rodriguez Aguilera Bazan A Rando Tous A Hidalgo Togores L De La Pena Barthel J | 2010 | Arch Esp Urol2010，63，10： | 1 |
| 10 | The ubiquitin proteasome pathway is required for processing the NF kappa B1 precursor protein and the activation of NF kappa B显示文摘 | PALOMBELLA V J RANDO O J GOLDBERG A L MANIATIS T | 1994 | Cell1994，78，5： | 1 |
| 11 | A review on large deployable structurefor astrophysics missions显示文摘 | Puig L Barton A Rando N | 2010 | Acta Astronautica2010，67，12： | 1 |
| 12 | Mutations in casein genes显示文摘 | Rando A Ramunno L Masina P | 2000 | Zootecnica E Nutrizatione Animale2000，26，： | 1 |
| 13 | Issue in implementing the C+ + binding to SDAI显示文摘 | RANDO T MCCABE L | 1994 | Computer Standard & Interface1994，16，4： | 1 |
| 14 | Classification of Marsala wines according to their polyphenol, carbohydrate and heavy metal levels using canonical discriminant analysis显示文摘 | Torre L La Pera G L Rando L | 2008 | Food Chemistry2008，110，3： | 1 |
| 15 | A review on large deployable structures for astrophysics missions 显示文摘 | Puig L Barton A Rando N | 2010 | Acta Astronautica2010，67，1： | 1 |
| 16 | A functional evolu- tionary approach to identify determinants of nucleosome posi- tioning: a unifying model for establishing the genome-wide pattern显示文摘 | HUGHES A L JIN Y RANDO O J et d | 2012 | Molecular Cell2012，48，1： | 1 |
| 17 | A new experimental method for the measurement of the interfacial tension between immiscible fluids at zero bond number显示文摘 | PASSERONE A LIGG1ERI L RANDO N | 1991 | J Colloid Interface Sci1991，146，： | 1 |
| 18 | Focal adhesion kinase is essential for costamerogenesis in cultured skeletal muscle ceils 显示文摘 | Navaline L Quach Thomas A Rando P | 2006 | Developmental Biolog2006，293，： | 1 |
| 19 | A review on large deployable structure for astrophysics missions显示文摘 | PUIG L BARTON A RANDO N | 2010 | Acta Astronautica2010，67，12： | 1 |
| 20 | Catalytic growth of carbon microtubules with fullerene structure 显示文摘 | YOSHICLA M M RANDO L | 1993 | Appl Phy Lett1993，62，： | 1 |
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