Evidence map›Paper›PMID 18829747›Full record

ArticleJournal of virology2008

Identification of a residue in hepatitis C virus E2 glycoprotein that determines scavenger receptor BI and CD81 receptor dependency and sensitivity to neutralizing antibodies.

Joe Grove, Søren Nielsen, Jin Zhong, Margaret F Bassendine, Heidi E Drummer, Peter Balfe, Jane A McKeating

Abstract read
In one paragraph

Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
–field-weighted citation impact
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

87 citing papers in PubMed.

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27 more citing papers are in PubMed but not listed here.

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.

Joe GroveDivision of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Søren Nielsen
Jin Zhong
Margaret F Bassendine
Heidi E Drummer
Peter Balfe
Jane A McKeating

Funding

Functional analysis of hepatitis C virus glycoproteinsR01AI050798 · NIAID · UNIVERSITY OF BIRMINGHAM · PI MCKEATING, JANE A. · 2004 to 2008
$1.3M
Medical Research Council G0400802Medical Research Council G0502028Medical Research Council G0801976NIAID NIH HHS AI40034-14NIAID NIH HHS AI50798NIAID NIH HHS N01 AI040034NIAID NIH HHS R01 AI050798Wellcome Trust
6 · The paper itself

Abstract

Hepatitis C virus (HCV) infection is dependent on at least three coreceptors: CD81, scavenger receptor BI (SR-BI), and claudin-1. The mechanism of how these molecules coordinate HCV entry is unknown. In this study we demonstrate that a cell culture-adapted JFH-1 mutant, with an amino acid change in E2 at position 451 (G451R), has a reduced dependency on SR-BI. This altered receptor dependency is accompanied by an increased sensitivity to neutralization by soluble CD81 and enhanced binding of recombinant E2 to cell surface-expressed and soluble CD81. Fractionation of HCV by density gradient centrifugation allows the analysis of particle-lipoprotein associations. The cell culture-adapted mutation alters the relationship between particle density and infectivity, with the peak infectivity occurring at higher density than the parental virus. No association was observed between particle density and SR-BI or CD81 coreceptor dependence. JFH-1 G451R is highly sensitive to neutralization by gp-specific antibodies, suggesting increased epitope exposure at the virion surface. Finally, an association was observed between JFH-1 particle density and sensitivity to neutralizing antibodies (NAbs), suggesting that lipoprotein association reduces the sensitivity of particles to NAbs. In summary, mutation of E2 at position 451 alters the relationship between particle density and infectivity, disrupts coreceptor dependence, and increases virion sensitivity to receptor mimics and NAbs. Our data suggest that a balanced interplay between HCV particles, lipoprotein components, and viral receptors allows the evasion of host immune responses.

Indexed as

AnimalsAntibodiesAntibody SpecificityAntigens, CDCell LineCricetinaeHumansMutationProtein BindingScavenger Receptors, Class BSolubilityTetraspanin 28Viral Envelope ProteinsVirionAntibodiesAntigens, CDCD81 protein, humanglycoprotein E2, Hepatitis C virusScavenger Receptors, Class BTetraspanin 28Viral Envelope Proteins

Identifiers

PMID18829747
PMCPMC2593310

What OpenQuestion holds

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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.