Evidence map›Paper›PMID 34835053›Full record

ArticleViruses2021

In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors.

Shonisani Wendy Limani, Njabulo Mnyandu, Abdullah Ely, Reubina Wadee, Anna Kramvis, Patrick Arbuthnot, Mohube Betty Maepa

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Viruses, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 39% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. 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

7 authors at 3 institutions in 1 country.

Shonisani Wendy LimaniWits/SAMRC Antiviral Gene Therapy Research Unit, Health Sciences Faculty, School of Pathology, University of the Witwatersrand, Private Bag 3, WITS 2050, Johannesburg 2000, South Africa.
Njabulo MnyanduWits/SAMRC Antiviral Gene Therapy Research Unit, Health Sciences Faculty, School of Pathology, University of the Witwatersrand, Private Bag 3, WITS 2050, Johannesburg 2000, South Africa.
Abdullah ElyWits/SAMRC Antiviral Gene Therapy Research Unit, Health Sciences Faculty, School of Pathology, University of the Witwatersrand, Private Bag 3, WITS 2050, Johannesburg 2000, South Africa.
Reubina WadeeDepartment of Anatomical Pathology, Health Sciences Faculty, School of Pathology, University of the Witwatersrand, Private Bag 3, WITS 2050 and National Health Laboratory Services, P.O. Box 1038, Johannesburg 2000, South Africa.ORCID 0000-0002-5981-4450
Anna KramvisHepatitis Virus Diversity Research Unit, Health Sciences Faculty, School of Clinical Medicine, University of the Witwatersrand, Private Bag 3, WITS 2050, Johannesburg 2000, South Africa.ORCID 0000-0001-6006-3765
Patrick ArbuthnotWits/SAMRC Antiviral Gene Therapy Research Unit, Health Sciences Faculty, School of Pathology, University of the Witwatersrand, Private Bag 3, WITS 2050, Johannesburg 2000, South Africa.ORCID 0000-0003-4149-8995
Mohube Betty MaepaWits/SAMRC Antiviral Gene Therapy Research Unit, Health Sciences Faculty, School of Pathology, University of the Witwatersrand, Private Bag 3, WITS 2050, Johannesburg 2000, South Africa.
South African Medical Research Council · ZANational Health Laboratory Service · ZAUniversity of the Witwatersrand · ZA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The paucity of animal models that simulate the replication of the hepatitis B virus (HBV) is an impediment to advancing new anti-viral treatments. The work reported here employed recombinant adeno-associated viruses (AAVs) to model HBV subgenotype A1 and subgenotype D3 replication in vitro and in vivo. Infection with subgenotype A1 is endemic to parts of sub-Saharan Africa, and it is associated with a high risk of hepatocellular carcinoma. Recombinant AAV serotype 2 (AAV2) and 8 (AAV8) vectors bearing greater-than-genome-length sequences of HBV DNA from subgenotype A1 and D3, were produced. Transduced liver-derived cultured cells produced HBV surface antigen and core antigen. Administration of AAV8 carrying HBV subgenotype A1 genome (AAV8-A1) to mice resulted in the sustained production of HBV replication markers over a six-month period, without elevated inflammatory cytokines, expression of interferon response genes or alanine transaminase activity. Markers of replication were generally higher in animals treated with subgenotype D3 genome-bearing AAVs than in those receiving the subgenotype A1-genome-bearing vectors. To validate the use of the AAV8-A1 murine model for anti-HBV drug development, the efficacy of anti-HBV artificial primary-microRNAs was assessed. Significant silencing of HBV markers was observed over a 6-month period after administering AAVs. These data indicate that AAVs conveniently and safely recapitulate the replication of different HBV subgenotypes, and the vectors may be used to assess antivirals' potency.

Indexed as

Disease Models, AnimalVirus ReplicationAnimalsAntiviral AgentsCell LineDependovirusGene ExpressionGene SilencingGenetic VectorsGenotypeHepatitis B, ChronicHepatitis B Surface AntigensHepatitis B virusHumansLiverMiceAntiviral AgentsHepatitis B Surface AntigensMicroRNAsadeno-associated virusanti-viral gene therapyHBV mouse modelshepatitis B virus

Identifiers

PMID34835053
PMCPMC8618177
OpenAlexW3214307463

What OpenQuestion holds

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Registered trials

None linked

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.