Evidence map›Paper›PMID 23593007›Full record

ArticlePLoS pathogens2013

Lipid droplet-binding protein TIP47 regulates hepatitis C Virus RNA replication through interaction with the viral NS5A protein.

Dorothee A Vogt, Grégory Camus, Eva Herker, Brian R Webster, Chia-Lin Tsou, Warner C Greene, Tien-Sze Benedict Yen, Melanie Ott

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

69 citing papers in PubMed, 114 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. HCV NS3/4A protease relocalizes CCTα to viral replication sites, enhancing phosphatidylcholine synthesis and viral replication.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Emerging role of lipophagy in liver disorders.Molecular and cellular biochemistry · 2024
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Perilipins at a glance.Journal of cell science · 2022
    Article
  19. [Hepatitis B and C: mechanisms of virus-induced liver pathogenesis and tumorigenesis].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2022
    Review
  20. Article

9 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

8 authors at 3 institutions in 2 countries.

Dorothee A VogtGladstone Institute of Virology and Immunology, San Francisco, United States of America.
Grégory Camus
Eva Herker
Brian R Webster
Chia-Lin Tsou
Warner C Greene
Tien-Sze Benedict Yen
Melanie Ott
Gladstone Institutes · USUniversity of California, San Francisco · USSan Francisco VA Medical Center · US

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Holger Willenbring · 1986 to 2026
$30.7M
NRSA Hepatology Training GrantT32DK060414 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mandana Khalili, JACQUELYN J. MAHER · 2002 to 2026
$6.8M
Microbial Pathogenesis and Host DefenseT32AI060537 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joanne N. Engel · 2004 to 2026
$6.5M
Role of mitochondrial core protein in Hepatitis C Virus pathogenesisR03AI069090 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI OTT, MELANIE MARIA · 2007 to 2008
$193k
NIAID NIH HHS P30 AI027763NIAID NIH HHS R03 AI069090NIAID NIH HHS R056 AI069090NIAID NIH HHS T32 AI060537NIDDK NIH HHS P30 DK026743NIDDK NIH HHS T32 DK060414
6 · The paper itself

Abstract

The nonstructural protein NS5A has emerged as a new drug target in antiviral therapies for Hepatitis C Virus (HCV) infection. NS5A is critically involved in viral RNA replication that takes place at newly formed membranes within the endoplasmic reticulum (membranous web) and assists viral assembly in the close vicinity of lipid droplets (LDs). To identify host proteins that interact with NS5A, we performed a yeast two-hybrid screen with the N-terminus of NS5A (amino acids 1-31), a well-studied α-helical domain important for the membrane tethering of NS5A. Our studies identified the LD-associated host protein, Tail-Interacting Protein 47 (TIP47) as a novel NS5A interaction partner. Coimmunoprecipitation experiments in Huh7 hepatoma cells confirmed the interaction of TIP47 with full-length NS5A. shRNA-mediated knockdown of TIP47 caused a more than 10-fold decrease in the propagation of full-length infectious HCV in Huh7.5 hepatoma cells. A similar reduction was observed when TIP47 was knocked down in cells harboring an autonomously replicating HCV RNA (subgenomic replicon), indicating that TIP47 is required for efficient HCV RNA replication. A single point mutation (W9A) in NS5A that disrupts the interaction with TIP47 but preserves proper subcellular localization severely decreased HCV RNA replication. In biochemical membrane flotation assays, TIP47 cofractionated with HCV NS3, NS5A, NS5B proteins, and viral RNA, and together with nonstructural viral proteins was uniquely distributed to lower-density LD-rich membrane fractions in cells actively replicating HCV RNA. Collectively, our data support a model where TIP47--via its interaction with NS5A--serves as a novel cofactor for HCV infection possibly by integrating LD membranes into the membranous web.

Indexed as

Virus ReplicationCell Line, TumorEndoplasmic ReticulumHEK293 CellsHepacivirusHepatitis CHumansLipidsPerilipin-3Point MutationRNA-Dependent RNA PolymeraseRNA InterferenceRNA, Small InterferingRNA, ViralVesicular Transport ProteinsViral Nonstructural ProteinsLipidsNS-5 protein, hepatitis C virusPerilipin-3PLIN3 protein, humanRNA-Dependent RNA PolymeraseRNA, Small InterferingRNA, ViralVesicular Transport ProteinsViral Nonstructural Proteins

Identifiers

PMID23593007
PMCPMC3623766
OpenAlexW1971435934

What OpenQuestion holds

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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.