Evidence map›Paper›PMID 25393308›Full record

ArticlePLoS computational biology2014

Inferring viral dynamics in chronically HCV infected patients from the spatial distribution of infected hepatocytes.

Frederik Graw, Ashwin Balagopal, Abraham J Kandathil, Stuart C Ray, David L Thomas, Ruy M Ribeiro, Alan S Perelson

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.4field-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

34 citing papers in PubMed, 50 citations in OpenAlex.

  1. Trial
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  6. Spatially structured models of viral dynamics: a scoping review.Microbiology and molecular biology reviews : MMBR · 2025
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  20. Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence.Proceedings of the National Academy of Sciences of the United States of America · 2018
    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

7 authors at 3 institutions in 2 countries.

Frederik GrawLos Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, New Mexico, United States of America; Center for Modeling and Simulation in the Biosciences, Heidelberg University, Heidelberg, Germany.
Ashwin BalagopalDepartment of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Abraham J KandathilDepartment of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Stuart C RayDepartment of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
David L ThomasDepartment of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Ruy M RibeiroLos Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, New Mexico, United States of America.
Alan S PerelsonLos Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, New Mexico, United States of America.
Johns Hopkins University · USLos Alamos National Laboratory · USJohns Hopkins Medicine · US

Funding

Vaccine Response and Immunotherapeutics SWGP30AI094189 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Richard E. Chaisson · 2012 to 2026
$67.0M
Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jiang Qian · 1985 to 2026
$22.1M
The Progression of Hepatitis C Among IDUs with HIVR01DA016078 · NIDA · JOHNS HOPKINS UNIVERSITY · PI BALAGOPAL, ASHWIN, THOMAS, DAVID L · 2002 to 2016
$10.9M
Collaborative Integration of HCV Molecular Virology and Mathematical ModelingR01AI078881 · NIAID · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PERELSON, ALAN S, UPRICHARD, SUSAN L. · 2011 to 2025
$7.5M
Modeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0M
COBRE Center for Evolutionary and Theoretical ImmunologyP20GM103452 · NIGMS · UNIVERSITY OF NEW MEXICO · PI LOKER, ERIC SAMUEL · 2012 to 2013
$4.2M
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
Viral kinetic models of HCV clearance in hemophiliacs treated with telaprevirR34HL109334 · NHLBI · UNIVERSITY OF CINCINNATI · PI SHERMAN, KENNETH E · 2012 to 2013
$713k
HIV, Kupffer Cells, and HCV-related Liver FibrosisK08AI081544 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BALAGOPAL, ASHWIN · 2009 to 2013
$644k
Collaborative Integration of HCV Molecular Virology and Mathematical ModelingR56AI078881 · NIAID · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PERELSON, ALAN S, UPRICHARD, SUSAN L. · 2010 to 2010
$421k
NEI NIH HHS EY001765NEI NIH HHS P30 EY001765NHLBI NIH HHS HL109334NHLBI NIH HHS R34 HL109334NIAID NIH HHS AI028433NIAID NIH HHS AI078881NIAID NIH HHS AI081544NIAID NIH HHS K08 AI081544NIAID NIH HHS P30 AI094189NIAID NIH HHS R01 AI028433NIAID NIH HHS R01 AI078881NIAID NIH HHS R37 AI028433NIAID NIH HHS R56 AI078881NIDA NIH HHS DA016078NIDA NIH HHS R01 DA016078NIGMS NIH HHS GM103452NIGMS NIH HHS P20 GM103452NIH HHS OD011095NIH HHS R01 OD011095
6 · The paper itself

Abstract

Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, we are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from 4-50 infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.

Indexed as

AdultAlgorithmsComputational BiologyFemaleHepacivirusHepatitis CHepatocytesHost-Pathogen InteractionsHumansLaser Capture MicrodissectionLiverMaleMiddle AgedModels, BiologicalSingle-Cell Analysis

Identifiers

PMID25393308
PMCPMC4230741
OpenAlexW2001444622

What OpenQuestion holds

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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.