Evidence map›Paper›PMID 19369346›Full record

ArticleJournal of virology2009

Modeling subgenomic hepatitis C virus RNA kinetics during treatment with alpha interferon.

Harel Dahari, Bruno Sainz, Alan S Perelson, Susan L Uprichard

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

42 citing papers in PubMed, 65 citations in OpenAlex.

  1. Trial
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  4. Review
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  11. Advanced Hepatitis C Virus Replication PDE Models within a Realistic Intracellular Geometric Environment.International journal of environmental research and public health · 2019
    Article
  12. Review
  13. Article
  14. Article
  15. A Robust and Efficient Numerical Method for RNA-Mediated Viral Dynamics.Frontiers in applied mathematics and statistics · 2017
    Article
  16. Article
  17. Article
  18. Article
  19. Article
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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

4 authors at 2 institutions in 1 country.

Harel DahariDepartment of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Bruno Sainz
Alan S Perelson
Susan L Uprichard
University of Illinois Chicago · USLos Alamos National Laboratory · US

Funding

MODELING VIRAL AND T LYMPHOCYTE DYNAMICSR01RR006555 · NCRR · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 1991 to 2011
$3.9M
Immune System Modeling/HIVR01AI028433 · NIAID · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 1990 to 2021
$3.7M
Immune System Modeling/HIVR37AI028433 · NIAID · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 2002 to 2011
$2.4M
High Throughput in vitro Hepatitis C Virus ScreeningR01AI070827 · NIAID · UNIVERSITY OF ILLINOIS AT CHICAGO · PI UPRICHARD, SUSAN L. · 2006 to 2009
$887k
NCRR NIH HHS R01 RR006555NCRR NIH HHS RR06555NIAID NIH HHS AI070827NIAID NIH HHS AI28433NIAID NIH HHS R01 AI028433NIAID NIH HHS R01 AI070827NIAID NIH HHS R37 AI028433
6 · The paper itself

Abstract

Although replicons have been used to demonstrate hepatitis C virus (HCV) inhibition by alpha interferon (IFN-alpha), the detailed inhibition kinetics required to mathematically model HCV RNA decline have been lacking. Therefore, we measured genotype 1b subgenomic replicon (sg1b) RNA levels under various IFN-alpha concentrations to assess the inhibition kinetics of intracellular HCV RNA. During nine days of IFN-alpha treatment, sg1b RNA decreased in a biphasic, dose-dependent manner. Using frequent measurements to dissect these phases during IFN-alpha treatments of 100 and 250 U/ml revealed that the first-phase sg1b RNA decline began approximately 12 h posttreatment, continued for 2 to 4 days, and then exhibited a distinct flat or slower second phase. Based on these data, we developed a mathematical model of IFN-alpha-induced intracellular sg1b RNA decline, and we show that the mechanism(s) mediating IFN-alpha inhibition of HCV acts primarily by reducing sg1b RNA amplification, with an additional effect on HCV RNA stability/degradation detectable at a dose of 250 U/ml IFN-alpha. While the extremely slow or flat second phase of viral RNA inhibition observed in vitro, in which there is little or no cell death, supports the in vivo modeling prediction that the more profound second-phase decline observed in IFN-alpha-treated patients reflects immune-mediated death/loss of productively infected cells, the second-phase decline in viral RNA with a dose of 250 U/ml IFN-alpha suggests that a further inhibition of intracellular HCV RNA levels may contribute as well. As such, dissection of HCV IFN-alpha inhibition kinetics in vitro has brought us closer to understanding the mechanism(s) by which IFN-alpha may be inhibiting HCV in vivo.

Indexed as

Cell LineHepacivirusHumansInterferon-alphaKineticsModels, TheoreticalRNA, ViralTime FactorsVirus ReplicationInterferon-alphaRNA, Viral

Identifiers

PMID19369346
PMCPMC2698578
OpenAlexW2107467541

What OpenQuestion 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 OpenQuestion graph.