Evidence map›Paper›PMID 27083116›Full record

ArticleAntiviral research2016

Characterization of novel hepadnaviral RNA species accumulated in hepatoma cells treated with viral DNA polymerase inhibitors.

Pinghu Zhang, Fei Liu, Fang Guo, Qiong Zhao, Jinhong Chang, Ju-Tao Guo

Open access · greenAbstract read
In one paragraph

Article in Antiviral research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 11% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
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  4. [Expert consensus on measurement and clinical application of serum HBV RNA in patients with chronic HBV infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022
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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

6 authors at 2 institutions in 2 countries.

Pinghu ZhangJiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Baruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA.
Fei LiuBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA.
Fang GuoBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA.
Qiong ZhaoBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA.
Jinhong ChangBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA.
Ju-Tao GuoBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USA. Electronic address: ju-tao.guo@bblumberg.org.
Hepatitis B Foundation · USChina Pharmaceutical University · CN

Funding

Evaulation of therapeutic benefits of HBV nucleocapsid assembly inhibitorsR01AI113267 · NIAID · DREXEL UNIVERSITY · PI DU, YANMING, GUO, JU-TAO · 2014 to 2018
$2.9M
NIAID NIH HHS R01 AI113267
6 · The paper itself

Abstract

Inhibitors of hepadnaviral DNA polymerases are predicted to inhibit both minus and plus strand of viral DNA synthesis and arrest viral DNA replication at the stage of pregenomic (pg) RNA-containing nucleocapsids. However, analyses of the RNA species of human and duck hepatitis B viruses (HBV and DHBV, respectively) in hepatoma cells treated with viral DNA polymerase inhibitors revealed the genesis of novel RNA species migrating slightly faster than the full-length pgRNA. The DNA polymerase inhibitor-induced accumulation of these RNA species were abolished in the presence of alpha-interferon or HBV nucleocapsid assembly inhibitors. Moreover, they were protected from microccocal nuclease digestion and devoid of a poly-A tail. These characteristics suggest that the novel RNA species are most likely generated from RNase H cleavage of encapsidated pgRNA, after primer translocation and synthesis of the 5' terminal portion of minus strand DNA. In support of this hypothesis, DNA polymerase inhibitor treatment of chicken hepatoma cells transfected with a DHBV genome encoding an RNase H inactive DNA polymerase (E696H) failed to produce such RNA species. Our results thus suggest that the currently available DNA polymerase inhibitors do not efficiently arrest minus strand DNA synthesis at the early stage in hepatocytes. Hence, development of novel antiviral agents that more potently suppress viral DNA synthesis or viral nucleocapsid assembly inhibitors that are mechanistically complementary to the currently available DNA polymerase inhibitors are warranted.

Indexed as

Antiviral AgentsCarcinoma, HepatocellularCell LineDNA-Directed DNA PolymeraseDNA ReplicationDNA, ViralHepatitis B virusHepatitis B Virus, DuckHumansInterferon-alphaLiver NeoplasmsNucleic Acid Synthesis InhibitorsNucleocapsidRibonuclease HRNARNA, ViralAntiviral AgentsDNA-Directed DNA PolymeraseDNA, ViralInterferon-alphaNucleic Acid Synthesis InhibitorspgRNARibonuclease HRNARNA, Viral

Identifiers

PMID27083116
PMCPMC5436692
OpenAlexW2339000844

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.