Evidence map›Paper›PMID 16378961›Full record

ArticleJournal of virology2006

Point mutations upstream of hepatitis B virus core gene affect DNA replication at the step of core protein expression.

Michael Guarnieri, Kyun-Hwan Kim, Genie Bang, Jisu Li, Yonghong Zhou, Xiaoli Tang, Jack Wands, Shuping Tong

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

27 citing papers in PubMed, 52 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Michael GuarnieriThe Liver Research Center and Brown Medical School, Providence, RI 02903, USA.
Kyun-Hwan Kim
Genie Bang
Jisu Li
Yonghong Zhou
Xiaoli Tang
Jack Wands
Shuping Tong
Brown University · US

Funding

WNT SIGNALING IN HEPATOCELLULAR CARCINOMAP20RR015578 · NCRR · BROWN UNIVERSITY · PI THOMPSON, WILLIAM ALBERT · 2000 to 2009
$22.8M
PATHOGENESIS, IMMUNODIAGNOSIS AND THERAPY OF HCCR37CA035711 · NCI · RHODE ISLAND HOSPITAL (PROVIDENCE, RI) · PI WANDS, JACK R · 2000 to 2008
$2.9M
Molecular Target(s) for Interruption of HBV InfectionR01CA109733 · NCI · RHODE ISLAND HOSPITAL · PI LI, JISU · 2005 to 2009
$1.1M
Hepatitis C virus core protein and cell proliferationR21DK066950 · NIDDK · RHODE ISLAND HOSPITAL · PI LI, JISU · 2004 to 2005
$308k
Replication and secretion of hepatitis B virus variantsR21DK062857 · NIDDK · RHODE ISLAND HOSPITAL (PROVIDENCE, RI) · PI TONG, SHUPING · 2003 to 2004
$308k
Hepatitis B virus e antigen expressionR03AI054535 · NIAID · RHODE ISLAND HOSPITAL (PROVIDENCE, RI) · PI TONG, SHUPING · 2003 to 2004
$154k
PATHOGENESIS, IMMUNODIAGNOSIS, AND THERAPY OF HCCR01CA035711 · NCI · RHODE ISLAND HOSPITAL (PROVIDENCE, RI) · PI WANDS, JACK R · 1985 to 1999
–
NCI NIH HHS CA109733NCI NIH HHS CA35711NCI NIH HHS R01 CA035711NCI NIH HHS R01 CA109733NCI NIH HHS R37 CA035711NCRR NIH HHS P20RR15578NIAID NIH HHS AI54535NIAID NIH HHS R03 AI054535NIDDK NIH HHS DK62857NIDDK NIH HHS DK66950NIDDK NIH HHS R21 DK062857NIDDK NIH HHS R21 DK066950
6 · The paper itself

Abstract

The pregenomic RNA directs replication of the hepatitis B virus (HBV) genome by serving both as the messenger for core protein and polymerase and as the genome precursor following its packaging into the core particle. RNA packaging is mediated by a stem-loop structure present at its 5' end designated the epsilon signal, which includes the core gene initiator AUG. The precore RNA has a slightly extended 5' end to cover the entire precore region and, consequently, directs the translation of a precore/core protein, which is secreted as e antigen (HBeAg) following removal of precore-derived signal peptide and the carboxyl terminus. A naturally occurring G1862T mutation upstream of the core AUG affects the bulge of the epsilon signal and generates a "forbidden" residue at the -3 position of the signal peptide cleavage site. Transfection of this and other mutants into human hepatoma cells failed to prove their inhibition of HBeAg secretion but rather revealed great impairment of genome replication. This replication defect was associated with reduced expression of core protein and could be overcome by a G1899A covariation, or by nonsense or frameshift mutation in the precore region. All these mutations antagonized the G1862T mutation on core protein expression. Cotransfection of the G1862T mutant with a replication-deficient HBV genome that provides core protein in trans also restored genome replication. Consistent with our findings in cell culture, HBV genotype A found in African/Asian patients has T1862 and is associated with much lower viremia titers than the European subgroup of genotype A.

Indexed as

Gene Expression Regulation, ViralAmino Acid SequenceDNA, ViralDown-RegulationHepatitis B e AntigensHepatitis B virusHumansMolecular Sequence DataMutationNucleic Acid ConformationViral Core ProteinsViral Envelope ProteinsVirus ReplicationDNA, ViralHepatitis B e AntigensViral Core ProteinsViral Envelope Proteins

Identifiers

PMID16378961
PMCPMC1346833
OpenAlexW2127584857

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.