ArticlePloS one2012
Ultra-deep pyrosequencing detects conserved genomic sites and quantifies linkage of drug-resistant amino acid changes in the hepatitis B virus genome.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- A dual recombinant strategy to quantify PreS1 antibody in hepatitis B patients with genotype B or C virus by ELISA.iScience · 2026Article
- Single-Cell Hepatitis B Sequencing Reveals Distinct Viral Infection Events Consistent With Superinfection.The Journal of infectious diseases · 2026Article
- Understanding Basic Concepts of Viral Quasispecies: From Evolutionary Dynamics to Clinical Relevance.Pathogens (Basel, Switzerland) · 2026Review
- Machine-learning based patient classification using Hepatitis B virus full-length genome quasispecies from Asian and European cohorts.Scientific reports · 2019Article
- Insights From Deep Sequencing of the HBV Genome-Unique, Tiny, and Misunderstood.Gastroenterology · 2019Review
- HBV quasispecies composition in Lamivudine-failed chronic hepatitis B patients and its influence on virological response to Tenofovir-based rescue therapy.Scientific reports · 2017Article
- Article
- A deep sequencing reveals significant diversity among dominant variants and evolutionary dynamics of avian leukosis viruses in two infectious ecosystems.BMC veterinary research · 2016Article
- Analysis of Quasispecies of Avain Leukosis Virus Subgroup J Using Sanger and High-throughput Sequencing.Virology journal · 2016Article
- Implementation of Next-Generation Sequencing for Hepatitis B Virus Resistance Testing and Genotyping in a Clinical Microbiology Laboratory.Journal of clinical microbiology · 2016Article
- Article
- Composition and Interactions of Hepatitis B Virus Quasispecies Defined the Virological Response During Telbivudine Therapy.Scientific reports · 2015Article
- Advanced molecular surveillance of hepatitis C virus.Viruses · 2015Review
- Article
- Extensive recombination due to heteroduplexes generates large amounts of artificial gene fragments during PCR.PloS one · 2014Article
- Prevalence of WHO transmitted drug resistance mutations by deep sequencing in antiretroviral-naïve subjects in Hunan Province, China.PloS one · 2014Article
- rtM204Q may serve as a novel lamivudine-resistance-associated mutation of hepatitis B virus.PloS one · 2014Article
- Comparison of next-generation sequencing and clone-based sequencing in analysis of hepatitis B virus reverse transcriptase quasispecies heterogeneity.Journal of clinical microbiology · 2013Article
- Quasispecies structure, cornerstone of hepatitis B virus infection: mass sequencing approach.World journal of gastroenterology · 2013Review
- Ultrasensitive amplification refractory mutation system real-time PCR (ARMS RT-PCR) assay for detection of minority hepatitis B virus-resistant strains in the era of personalized medicine.Journal of clinical microbiology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSelection of amino acid substitutions associated with resistance to nucleos(t)ide-analog (NA) therapy in the hepatitis B virus (HBV) reverse transcriptase (RT) and their combination in a single viral genome complicates treatment of chronic HBV infection and may affect the overlapping surface coding region. In this study, the variability of an overlapping polymerase-surface region, critical for NA resistance, is investigated before treatment and under antiviral therapy, with assessment of NA-resistant amino acid changes simultaneously occurring in the same genome (linkage analysis) and their influence on the surface coding region. METHODOLOGY/PRINCIPAL
findingsSerum samples obtained from chronic HBV-infected patients at pre-treatment and during sequential NA treatment with lamivudine, adefovir, and entecavir were analyzed by ultra-deep pyrosequencing (UDPS) using the GS-FLX platform (454 Life Sciences-Roche). The pre-treatment HBV quasispecies was not enriched with NA-resistant substitutions. The frequencies of this type of substitutions at pre-treatment did not predict the frequencies observed during lamivudine treatment. On linkage analysis of the RT region studied, NA-resistant HBV variants (except for rtA181T) were present in combinations of amino acid substitutions that increased in complexity after viral breakthrough to entecavir, at which time the combined variant rtL180M-S202G-M204V-V207I predominated. In the overlapping surface region, NA-resistant substitutions caused selection of stop codons in a significant percentage of sequences both at pre-treatment and during sequential treatment; the rtA181T substitution, related to sW172stop, predominated during treatment with lamivudine and adefovir. A highly conserved RT residue (rtL155), even more conserved than the essential residues in the RT catalytic motif YMDD, was identified in all samples.
conclusionsUDPS methodology enabled quantification of HBV quasispecies variants, even those harboring complex combinations of amino acid changes. The high percentage of potentially defective genomes, especially in the surface region, suggests effective trans-complementation of these variants.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.