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

Padmanabhan, Pranesh and Garaigorta, Urtzi and Dixit, Narendra M (2014) Emergent properties of the interferon-signalling network may underlie the success of hepatitis C treatment. In: NATURE COMMUNICATIONS, 5 .

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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.

Item Type:	Journal Article
Publication:	NATURE COMMUNICATIONS
Publisher:	NATURE PUBLISHING GROUP
Additional Information:	Copyright for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre:	Division of Mechanical Sciences > Chemical Engineering
Date Deposited:	25 Jul 2014 04:38
Last Modified:	25 Jul 2014 04:38
URI:	http://eprints.iisc.ac.in/id/eprint/49517

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