Emergent properties of the interferon-signalling network may underlie the success of hepatitis C treatment

Padmanabhan, Pranesh, Garaigorta, Urtzi and Dixit, Narendra M. (2014) Emergent properties of the interferon-signalling network may underlie the success of hepatitis C treatment. Nature Communications, 5 1-9. doi:10.1038/ncomms4872

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Author Padmanabhan, Pranesh
Garaigorta, Urtzi
Dixit, Narendra M.
Title Emergent properties of the interferon-signalling network may underlie the success of hepatitis C treatment
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2014-05-16
Sub-type Article (original research)
DOI 10.1038/ncomms4872
Open Access Status File (Publisher version)
Volume 5
Start page 1
End page 9
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2015
Language eng
Abstract Current interferon alpha-based treatment of hepatitis C virus (HCV) infection fails to cure a sizeable fraction of patients treated. The cause of this treatment failure remains unknown. Here using mathematical modelling, we predict treatment failure to be a consequence of the emergent properties of the interferon-signalling network. HCV induces bistability in the network, creating a new steady state where it can persist. Cells that admit the new steady state alone are refractory to interferon. Using a model of viral kinetics, we show that when the fraction of cells refractory to interferon in a patient exceeds a critical value, treatment fails. Direct-acting antivirals that suppress HCV replication can eliminate the new steady state, restoring interferon sensitivity and improving treatment response. Our study thus presents a new conceptual basis of HCV persistence and treatment response, elucidates the origin of the synergy between interferon and direct-acting antivirals, and facilitates rational treatment optimization.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 5 times in Scopus Article | Citations
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Created: Sat, 13 Jun 2015, 12:09:47 EST by Pranesh Padmanabhan on behalf of Scholarly Communication and Digitisation Service