Evidence map›Paper›PMID 23300734›Full record

ArticlePloS one2012

Interplay between basic residues of hepatitis C virus glycoprotein E2 with viral receptors, neutralizing antibodies and lipoproteins.

George Koutsoudakis, Jakub Dragun, Sofia Pérez-Del-Pulgar, Mairene Coto-Llerena, Laura Mensa, Gonzalo Crespo, Patricia González, Miquel Navasa, Xavier Forns

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

14 citing papers in PubMed, 20 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

9 authors at 1 institution in 1 country.

George KoutsoudakisLiver Unit, Hospital Clínic, Institut D'Investigacions Biomèdics August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. gkoutsou@clinic.ub.es
Jakub Dragun
Sofia Pérez-Del-Pulgar
Mairene Coto-Llerena
Laura Mensa
Gonzalo Crespo
Patricia González
Miquel Navasa
Xavier Forns
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Positively-charged amino acids are located at specific positions in the envelope glycoprotein E2 of the hepatitis C virus (HCV): two histidines (H) and four arginines (R) in two conserved WHY and one RGERCDLEDRDR motifs, respectively. Additionally, the E2 hypervariable region 1 (HVR1) is rich in basic amino acids. To investigate the role(s) of these residues in HCV entry, we subjected to comparative infection and sedimentation analysis cell culture-produced (HCVcc, genotype 2a) wild type virus, a panel of alanine single-site mutants and a HVR1-deletion variant. Initially, we analyzed the effects of these mutations on E2-heparan sulfate (HS) interactions. The positive milieu of the HVR1, formulated by its basic amino acids (key residues the conserved H³⁸⁶ and R⁴⁰⁸), and the two highly conserved basic residues H⁴⁸⁸ and R⁶⁴⁸ contributed to E2-HS interactions. Mutations in these residues did not alter the HCVcc-CD81 entry, but they modified the HCVcc-scavenger receptor class B type I (SR-BI) dependent entry and the neutralization by anti-E2 or patients IgG. Finally, separation by density gradients revealed that mutant viruses abolished partially or completely the infectivity of low density particles, which are believed to be associated with lipoproteins. This study shows that there exists a complex interplay between the basic amino acids located in HVR1 and other conserved E2 motifs with the HS, the SR-BI, and neutralizing antibodies and suggests that HCV-associated lipoproteins are implicated in these interactions.

Indexed as

Amino Acid MotifsAmino Acids, BasicAmino Acid SequenceAmino Acid SubstitutionAntibodies, NeutralizingAntibodies, ViralBinding SitesCell LineHepacivirusHeparinHepatitis C, ChronicHost-Pathogen InteractionsHumansImmunoglobulin GLipoproteinsMolecular Sequence DataAmino Acids, BasicAntibodies, NeutralizingAntibodies, Viralglycoprotein E2, Hepatitis C virusHeparinImmunoglobulin GLipoproteinsSCARB1 protein, humanScavenger Receptors, Class BViral Envelope Proteins

Identifiers

PMID23300734
PMCPMC3531341
OpenAlexW1987134275

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.