Evidence map›Paper›PMID 27128351›Full record

ArticleVirology2016

Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies.

Vyas Ramanan, Kartik Trehan, Mei-Lyn Ong, Joseph M Luna, Hans-Heinrich Hoffmann, Christine Espiritu, Timothy P Sheahan, Hamsika Chandrasekar, Robert E Schwartz, Kathleen S Christine and 3 more

Open access · greenAbstract read
In one paragraph

Article in Virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
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  11. Engineered Livers for Infectious Diseases.Cellular and molecular gastroenterology and hepatology · 2018
    Review
  12. 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

13 authors at 4 institutions in 2 countries.

Vyas RamananInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kartik TrehanInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mei-Lyn OngComputational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Joseph M LunaCenter for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, 10065 NY, USA.
Hans-Heinrich HoffmannCenter for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, 10065 NY, USA.
Christine EspirituCenter for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, 10065 NY, USA.
Timothy P SheahanCenter for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, 10065 NY, USA.
Hamsika ChandrasekarDepartment of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Robert E SchwartzInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kathleen S ChristineInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Charles M RiceCenter for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, 10065 NY, USA.
Alexander van OudenaardenDepartment of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Sangeeta N BhatiaInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: sbhatia@mit.edu.
Massachusetts Institute of Technology · USRockefeller University · USBrigham and Women's Hospital · USRoyal Netherlands Academy of Arts and Sciences · NL

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
TRANS-NETWORK PROJECTSU54CA143874 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI CHAKRABORTY, ARUP K. · 2009 to 2013
$15.1M
Modeling human hepatotropic infections in complex tissue organoidsR01DK085713 · NIDDK · ROCKEFELLER UNIVERSITY · PI BHATIA, SANGEETA N., RICE, CHARLES M · 2009 to 2013
$5.6M
Structure and function of the HCV RNA replicaseR01CA057973 · NCI · WASHINGTON UNIVERSITY · PI RICE, CHARLES M · 1992 to 2013
$4.7M
Hepatitis C antivirals: Mechanism of action, combination efficacy and resistanceR01AI099284 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2012 to 2016
$3.6M
Stochastic gene expression in differentiation and developmentDP1OD003936 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI VAN OUDENAARDEN, ALEXANDER · 2008 to 2011
$3.4M
Impact of species-specific host responses on restriction of hepatotropic virusesR21AI117213 · NIAID · PRINCETON UNIVERSITY · PI PLOSS, ALEXANDER, SCHWARTZ, ROBERT E · 2015 to 2016
$471k
Howard Hughes Medical InstituteNCI NIH HHS P30 CA014051NCI NIH HHS R01 CA057973NCI NIH HHS U54 CA143874NIAID NIH HHS R01 AI099284NIAID NIH HHS R21 AI117213NIDDK NIH HHS R01 DK085713NIH HHS DP1 OD003936
6 · The paper itself

Abstract

Hepatitis C virus (HCV) is a positive single-stranded RNA virus of enormous global health importance, with direct-acting antiviral therapies replacing an immunostimulatory interferon-based regimen. The dynamics of HCV positive and negative-strand viral RNAs (vRNAs) under antiviral perturbations have not been studied at the single-cell level, leaving a gap in our understanding of antiviral kinetics and host-virus interactions. Here, we demonstrate quantitative imaging of HCV genomes in multiple infection models, and multiplexing of positive and negative strand vRNAs and host antiviral RNAs. We capture the varying kinetics with which antiviral drugs with different mechanisms of action clear HCV infection, finding the NS5A inhibitor daclatasvir to induce a rapid decline in negative-strand viral RNAs. We also find that the induction of host antiviral genes upon interferon treatment is positively correlated with viral load in single cells. This study adds smFISH to the toolbox available for analyzing the treatment of RNA virus infections.

Indexed as

Genome, ViralMolecular ImagingAntiviral AgentsCell LineHepacivirusHepatitis CHost-Pathogen InteractionsHumansIn Situ Hybridization, FluorescenceMicroscopy, FluorescenceRNA, ViralSingle-Cell AnalysisViral Nonstructural ProteinsVirus ReplicationAntiviral AgentsRNA, ViralViral Nonstructural ProteinsHCVHost–virus interactionsSingle-molecule FISHViral replication

Identifiers

PMID27128351
PMCPMC5366982
OpenAlexW2342417544

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.