Evidence map›Paper›PMID 16105887›Full record

ArticleGut2006

Relation between viral fitness and immune escape within the hepatitis C virus protease.

J Söderholm, G Ahlén, A Kaul, L Frelin, M Alheim, C Barnfield, P Liljeström, O Weiland, D R Milich, R Bartenschlager and 1 more

Open access · greenAbstract read
In one paragraph

Article in Gut, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

47 citing papers in PubMed, 100 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. CD8Frontiers in immunology · 2022
    Article
  5. Review
  6. Article
  7. Expansion of Unique Hepatitis C Virus-Specific Public CD8Journal of immunology (Baltimore, Md. : 1950) · 2021
    Article
  8. Article
  9. Adaptive Immune Response against Hepatitis C Virus.International journal of molecular sciences · 2020
    Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Observational
  16. A targeted controlled force injection of genetic material in vivo.Molecular therapy. Methods & clinical development · 2016
    Article
  17. Article
  18. Review
  19. Article
  20. 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

11 authors at 1 institution in 1 country.

J SöderholmDivision of Clinical Virology, Karolinska Institutet at Karolinska University Hospital, S-141 86 Stockholm, Sweden.
G Ahlén
A Kaul
L Frelin
M Alheim
C Barnfield
P Liljeström
O Weiland
D R Milich
R Bartenschlager
M Sällberg
Karolinska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe hepatitis C virus (HCV) mutates within human leucocyte antigen (HLA) class I restricted immunodominant epitopes of the non-structural (NS) 3/4A protease to escape cytotoxic T lymphocyte (CTL) recognition and promote viral persistence. However, variability is not unlimited, and sometimes almost absent, and factors that restrict viral variability have not been defined experimentally.

aimsWe wished to explore whether the variability of the immunodominant CTL epitope at residues 1073-1081 of the NS3 protease was limited by viral fitness. PATIENTS: Venous blood was obtained from six patients (four HLA-A2+) with chronic HCV infection and from one HLA-A2+ patient with acute HCV infection.

methodsNS3/4A genes were amplified from serum, cloned in a eukaryotic expression plasmid, sequenced, and expressed. CTL recognition of naturally occurring and artificially introduced escape mutations in HLA-A2-restricted NS3 epitopes were determined using CTLs from human blood and genetically immunised HLA-A2-transgenic mice. HCV replicons were used to test the effect of escape mutations on HCV protease activity and RNA replication.

resultsSequence analysis of NS3/4A confirmed low genetic variability. The major viral species had functional proteases with 1073-1081 epitopes that were generally recognised by cross reactive human and murine HLA-A2 restricted CTLs. Introduction of mutations at five positions of the 1073-1081 epitope prevented CTL recognition but three of these reduced protease activity and RNA replication.

conclusionsViral fitness can indeed limit the variability of HCV within immunological epitopes. This helps to explain why certain immunological escape variants never appear as a major viral species in infected humans.

Indexed as

Immune ToleranceAcute DiseaseAdultAnimalsCytotoxicity, ImmunologicDEAD-box RNA HelicasesEpitopes, T-LymphocyteFemaleGenes, ViralGenetic VariationHepacivirusHepatitis CHepatitis C, ChronicHLA-A2 AntigenHumansImmunodominant EpitopesDEAD-box RNA HelicasesEpitopes, T-LymphocyteHLA-A2 AntigenImmunodominant EpitopesNS3 protein, hepatitis C virusNucleoside-TriphosphatasePeptide FragmentsRNA, ViralSerine EndopeptidasesViral Nonstructural ProteinsViral Proteases

Identifiers

PMID16105887
PMCPMC1856491
OpenAlexW2152786092

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.