Evidence map›Paper›PMID 26658490›Full record

ArticlePloS one2015

The Hepatitis B Virus Genotype Affects the Persistence of Viral Replication in Immunodeficient NOG Mice.

Yoshinobu Yokoyama, Takuya Miyagi, Hayato Hikita, Teppei Yoshioka, Kaori Mukai, Takatoshi Nawa, Ryotaro Sakamori, Kazuyoshi Ohkawa, Naoki Hiramatsu, Takeshi Takahashi and 4 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 31% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Yoshinobu YokoyamaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takuya MiyagiDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Hayato HikitaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Teppei YoshiokaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kaori MukaiDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takatoshi NawaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Ryotaro SakamoriDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kazuyoshi OhkawaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Naoki HiramatsuDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takeshi TakahashiLaboratory Animal Research Department, Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
Hiroshi SuemizuLaboratory Animal Research Department, Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
Akihide RyoDepartment of Microbiology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
Tomohide TatsumiDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Tetsuo TakeharaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Osaka University · JPCentral Institute for Experimental Animals · JPYokohama City University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsAt least eight genotypes of Hepatitis B virus (HBV) have been identified. HBV genotype C is the most common genotype in Japan, although the incidence of HBV genotype A is increasing. The reason underlying the differences in viral multiplication of the HBV genotypes is unclear, especially in vivo. The purpose of this study was to elucidate the differences in HBV load and the persistence of viremia in vivo between genotypes A and C.

methodsImmunodeficient NOG mice were transfected by hydrodynamic injection with the HBV expression plasmids pHBA1.2 or pHBC1.2, which contain overlength (1.2-mer) copies of the genomes of HBV genotype A or C, respectively.

resultsOne day after transfection, the number of HBcAg-positive hepatocytes and serum HBV DNA levels were similar between mice transfected with pHBA1.2 and pHBC1.2. Serum levels of HBV DNA, HBsAg and HBeAg in mice transfected with pHBA1.2 were maintained over 5 months. In contrast, those in mice with pHBC1.2 gradually decreased over time and reached undetectable levels within 3 months after transfection. HBcAg-stained hepatocytes were detected in mice transfected with pHBA1.2, but not pHBC1.2, 5 months post-transfection. Double-staining immunohistochemistry revealed that the number of cleaved caspase3-stained, HBcAg-positive hepatocytes in the pHBC1.2-transfected mice was higher than in the pHBA1.2-transfected mice 3 days post-transfection. Moreover, the plasmid DNA and covalently closed circular DNA levels were decreased in the livers of pHBC1.2-transfected mice. These results suggested that hepatocytes expressing HBV genotype C were eliminated by apoptosis in the absence of immune cells more often than in hepatocytes expressing HBV genotype A.

conclusionsImmunodeficient mice transfected with HBV genotype A develop persistent viremia, whereas those transfected with HBV genotype C exhibit transient viremia accompanied by apoptosis of HBV-expressing hepatocytes. This differences may affect the clinical courses of patients infected with HBV genotypes A and C.

Indexed as

AnimalsBlotting, WesternDNA, ViralGenotypeHepatitis B virusHepatocytesMaleMiceMice, Inbred StrainsReal-Time Polymerase Chain ReactionViral LoadViremiaVirus ReplicationDNA, Viral

Identifiers

PMID26658490
PMCPMC4682774
OpenAlexW2197775792

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LicenceCC BY
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Registered trials

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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.