Evidence map›Paper›PMID 28115001›Full record

ArticleVirology journal2017

Host Cell Copper Transporters CTR1 and ATP7A are important for Influenza A virus replication.

Jonathan C Rupp, Manon Locatelli, Alexis Grieser, Andrea Ramos, Patricia J Campbell, Hong Yi, John Steel, Jason L Burkhead, Eric Bortz

Open access · goldAbstract read
In one paragraph

Article in Virology journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
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  12. The Crossroads between Host Copper Metabolism and Influenza Infection.International journal of molecular sciences · 2021
    Review
  13. Herbal immune-boosters: Substantial warriors of pandemic Covid-19 battle.Phytomedicine : international journal of phytotherapy and phytopharmacology · 2021
    Review
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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 2 institutions in 2 countries.

Jonathan C RuppDepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, AK, USA.
Manon LocatelliDepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, AK, USA.
Alexis GrieserDepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, AK, USA.
Andrea RamosDepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, AK, USA.
Patricia J CampbellDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
Hong YiDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
John SteelDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
Jason L BurkheadDepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, AK, USA. jlburkhead@uaa.alaska.edu.
Eric BortzDepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, AK, USA. ebortz@uaa.alaska.edu.ORCID 0000-0002-1376-0012
University of Alaska Anchorage · USEmory University · US

Funding

The Administrative CoreP20GM103395 · NIGMS · UNIVERSITY OF ALASKA FAIRBANKS · PI BRIAN M BARNES · 2012 to 2026
$66.1M
NIAID NIH HHS HHSN272201400004CNIAID NIH HHS HHSN272201400008CNIGMS NIH HHS P20 GM103395
6 · The paper itself

Abstract

backgroundThe essential role of copper in eukaryotic cellular physiology is known, but has not been recognized as important in the context of influenza A virus infection. In this study, we investigated the effect of cellular copper on influenza A virus replication.

methodsInfluenza A/WSN/33 (H1N1) virus growth and macromolecule syntheses were assessed in cultured human lung cells (A549) where the copper concentration of the growth medium was modified, or expression of host genes involved in copper homeostasis was targeted by RNA interference.

resultsExogenously increasing copper concentration, or chelating copper, resulted in moderate defects in viral growth. Nucleoprotein (NP) localization, neuraminidase activity assays and transmission electron microscopy did not reveal significant defects in virion assembly, morphology or release under these conditions. However, RNAi knockdown of the high-affinity copper importer CTR1 resulted in significant viral growth defects (7.3-fold reduced titer at 24 hours post-infection, p = 0.04). Knockdown of CTR1 or the trans-Golgi copper transporter ATP7A significantly reduced polymerase activity in a minigenome assay. Both copper transporters were required for authentic viral RNA synthesis and NP and matrix (M1) protein accumulation in the infected cell.

conclusionsThese results demonstrate that intracellular copper regulates the influenza virus life cycle, with potentially distinct mechanisms in specific cellular compartments. These observations provide a new avenue for drug development and studies of influenza virus pathogenesis.

Indexed as

Host-Pathogen InteractionsVirus ReplicationAdenosine TriphosphatasesCation Transport ProteinsCell LineCopperCopper Transporter 1Copper-Transporting ATPasesCulture MediaEpithelial CellsHumansInfluenza A Virus, H1N1 SubtypeAdenosine TriphosphatasesATP7A protein, humanCation Transport ProteinsCopperCopper Transporter 1Copper-Transporting ATPasesCulture MediaSLC31A1 protein, humanATP7ACell metabolismCopperCopper transportCTR1Influenza virus

Identifiers

PMID28115001
PMCPMC5259989
OpenAlexW2580583255

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.