Evidence map›Paper›PMID 18579596›Full record

ArticleJournal of virology2008

Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity.

Michelle J Farquhar, Helen J Harris, Mandy Diskar, Sarah Jones, Christopher J Mee, Søren U Nielsen, Claire L Brimacombe, Sonia Molina, Geoffrey L Toms, Patrick Maurel and 5 more

Open access · greenAbstract 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 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
4.3field-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

50 citing papers in PubMed, 99 citations in OpenAlex.

  1. Article
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  4. Article
  5. GPharmacological reviews · 2021
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Viral journeys on the intracellular highways.Cellular and molecular life sciences : CMLS · 2018
    Review
  13. Article
  14. Article
  15. Relevance of Rab Proteins for the Life Cycle of Hepatitis C Virus.Frontiers in cell and developmental biology · 2018
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

15 authors at 6 institutions in 4 countries.

Michelle J FarquharDivision of Immunity and Infection, Hepatitis C Research Group, University of Birmingham, Birmingham, United Kingdom.
Helen J Harris
Mandy Diskar
Sarah Jones
Christopher J Mee
Søren U Nielsen
Claire L Brimacombe
Sonia Molina
Geoffrey L Toms
Patrick Maurel
John Howl
Friedrich W Herberg
Sven C D van Ijzendoorn
Peter Balfe
Jane A McKeating
University of Birmingham · GBInserm · FRNewcastle University · GBUniversity of Kassel · DEUniversity of Wolverhampton · GBUniversity Medical Center Groningen · NL

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 G0801976NIAID NIH HHS AI50798NIAID NIH HHS R01 AI050798Wellcome Trust
6 · The paper itself

Abstract

Viruses exploit signaling pathways to their advantage during multiple stages of their life cycle. We demonstrate a role for protein kinase A (PKA) in the hepatitis C virus (HCV) life cycle. The inhibition of PKA with H89, cyclic AMP (cAMP) antagonists, or the protein kinase inhibitor peptide reduced HCV entry into Huh-7.5 hepatoma cells. Bioluminescence resonance energy transfer methodology allowed us to investigate the PKA isoform specificity of the cAMP antagonists in Huh-7.5 cells, suggesting a role for PKA type II in HCV internalization. Since viral entry is dependent on the host cell expression of CD81, scavenger receptor BI, and claudin-1 (CLDN1), we studied the role of PKA in regulating viral receptor localization by confocal imaging and fluorescence resonance energy transfer (FRET) analysis. Inhibiting PKA activity in Huh-7.5 cells induced a reorganization of CLDN1 from the plasma membrane to an intracellular vesicular location(s) and disrupted FRET between CLDN1 and CD81, demonstrating the importance of CLDN1 expression at the plasma membrane for viral receptor activity. Inhibiting PKA activity in Huh-7.5 cells reduced the infectivity of extracellular virus without modulating the level of cell-free HCV RNA, suggesting that particle secretion was not affected but that specific infectivity was reduced. Viral particles released from H89-treated cells displayed the same range of buoyant densities as did those from control cells, suggesting that viral protein association with lipoproteins is not regulated by PKA. HCV infection of Huh-7.5 cells increased cAMP levels and phosphorylated PKA substrates, supporting a model where infection activates PKA in a cAMP-dependent manner to promote virus release and transmission.

Indexed as

Virus InternalizationAntigens, CDCarcinoma, HepatocellularCell LineCell Line, TumorClaudin-1Cyclic AMP-Dependent Protein KinasesFluorescent Antibody Technique, IndirectGenes, ReporterHepacivirusHumansIsoenzymesKidneyLiver NeoplasmsLuciferasesMembrane ProteinsAntigens, CDClaudin-1CLDN1 protein, humanCyclic AMP-Dependent Protein KinasesIsoenzymesLuciferasesMembrane ProteinsReceptors, VirusSCARB1 protein, humanScavenger Receptors, Class B

Identifiers

PMID18579596
PMCPMC2519651
OpenAlexW2171376829

What Socratic 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 Socratic graph.