Evidence map›Paper›PMID 25569684›Full record

ArticlePLoS pathogens2015

Identification of HNRNPK as regulator of hepatitis C virus particle production.

Marion Poenisch, Philippe Metz, Hagen Blankenburg, Alessia Ruggieri, Ji-Young Lee, Daniel Rupp, Ilka Rebhan, Kathrin Diederich, Lars Kaderali, Francisco S Domingues and 4 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

44 citing papers in PubMed, 62 citations in OpenAlex.

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  19. Beyond Autophagy: The Expanding Roles of ATG8 Proteins.Trends in biochemical sciences · 2021
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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

14 authors at 5 institutions in 2 countries.

Marion PoenischDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Philippe MetzDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Hagen BlankenburgDepartment of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbrücken, Germany; Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, Affiliated Institute of the University of Lübeck, Lübeck, Germany.
Alessia RuggieriDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Ji-Young LeeDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Daniel RuppDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Ilka RebhanDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Kathrin DiederichDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Lars KaderaliViroQuant Research Group Modeling, University of Heidelberg, Heidelberg, Germany; Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Francisco S DominguesCenter for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, Affiliated Institute of the University of Lübeck, Lübeck, Germany.
Mario AlbrechtDepartment of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbrücken, Germany.
Volker LohmannDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Holger ErfleViroQuant-CellNetworks RNAi Screening Facility, University of Heidelberg, Heidelberg, Germany.
Ralf BartenschlagerDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Heidelberg University · DEEurac Research · ITMax Planck Institute for Informatics · DETU Dresden · DEUniversity of Lübeck · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatitis C virus (HCV) is a major cause of chronic liver disease affecting around 130 million people worldwide. While great progress has been made to define the principle steps of the viral life cycle, detailed knowledge how HCV interacts with its host cells is still limited. To overcome this limitation we conducted a comprehensive whole-virus RNA interference-based screen and identified 40 host dependency and 16 host restriction factors involved in HCV entry/replication or assembly/release. Of these factors, heterogeneous nuclear ribonucleoprotein K (HNRNPK) was found to suppress HCV particle production without affecting viral RNA replication. This suppression of virus production was specific to HCV, independent from assembly competence and genotype, and not found with the related Dengue virus. By using a knock-down rescue approach we identified the domains within HNRNPK required for suppression of HCV particle production. Importantly, HNRNPK was found to interact specifically with HCV RNA and this interaction was impaired by mutations that also reduced the ability to suppress HCV particle production. Finally, we found that in HCV-infected cells, subcellular distribution of HNRNPK was altered; the protein was recruited to sites in close proximity of lipid droplets and colocalized with core protein as well as HCV plus-strand RNA, which was not the case with HNRNPK variants unable to suppress HCV virion formation. These results suggest that HNRNPK might determine efficiency of HCV particle production by limiting the availability of viral RNA for incorporation into virions. This study adds a new function to HNRNPK that acts as central hub in the replication cycle of multiple other viruses.

Indexed as

Cells, CulturedHEK293 CellsHepacivirusHeterogeneous-Nuclear Ribonucleoprotein KHumansProtein BindingRibonucleoproteinsRNA InterferenceRNA, Small InterferingRNA, ViralVirionVirus AssemblyVirus ReplicationHeterogeneous-Nuclear Ribonucleoprotein KHNRNPK protein, humanRibonucleoproteinsRNA, Small InterferingRNA, Viral

Identifiers

PMID25569684
PMCPMC4287573
OpenAlexW2071591548

What OpenQuestion holds

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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.