Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.

Hepatitis C virus (HCV) infection develops into chronicity in 80% of all patients, characterized by persistent low-level replication. To understand how the virus establishes its tightly controlled intracellular RNA replication cycle, we developed the first detailed mathematical model of the initial...

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Autores principales:	Marco Binder, Nurgazy Sulaimanov, Diana Clausznitzer, Manuel Schulze, Christian M Hüber, Simon M Lenz, Johannes P Schlöder, Martin Trippler, Ralf Bartenschlager, Volker Lohmann, Lars Kaderali
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e1dc895e827a4dd7b115633d1eeb9a6a
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spelling	oai:doaj.org-article:e1dc895e827a4dd7b115633d1eeb9a6a2021-11-18T06:07:45ZReplication vesicles are load- and choke-points in the hepatitis C virus lifecycle.1553-73661553-737410.1371/journal.ppat.1003561https://doaj.org/article/e1dc895e827a4dd7b115633d1eeb9a6a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23990783/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Hepatitis C virus (HCV) infection develops into chronicity in 80% of all patients, characterized by persistent low-level replication. To understand how the virus establishes its tightly controlled intracellular RNA replication cycle, we developed the first detailed mathematical model of the initial dynamic phase of the intracellular HCV RNA replication. We therefore quantitatively measured viral RNA and protein translation upon synchronous delivery of viral genomes to host cells, and thoroughly validated the model using additional, independent experiments. Model analysis was used to predict the efficacy of different classes of inhibitors and identified sensitive substeps of replication that could be targeted by current and future therapeutics. A protective replication compartment proved to be essential for sustained RNA replication, balancing translation versus replication and thus effectively limiting RNA amplification. The model predicts that host factors involved in the formation of this compartment determine cellular permissiveness to HCV replication. In gene expression profiling, we identified several key processes potentially determining cellular HCV replication efficiency.Marco BinderNurgazy SulaimanovDiana ClausznitzerManuel SchulzeChristian M HüberSimon M LenzJohannes P SchlöderMartin TripplerRalf BartenschlagerVolker LohmannLars KaderaliPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 8, p e1003561 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Marco Binder Nurgazy Sulaimanov Diana Clausznitzer Manuel Schulze Christian M Hüber Simon M Lenz Johannes P Schlöder Martin Trippler Ralf Bartenschlager Volker Lohmann Lars Kaderali Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.
description	Hepatitis C virus (HCV) infection develops into chronicity in 80% of all patients, characterized by persistent low-level replication. To understand how the virus establishes its tightly controlled intracellular RNA replication cycle, we developed the first detailed mathematical model of the initial dynamic phase of the intracellular HCV RNA replication. We therefore quantitatively measured viral RNA and protein translation upon synchronous delivery of viral genomes to host cells, and thoroughly validated the model using additional, independent experiments. Model analysis was used to predict the efficacy of different classes of inhibitors and identified sensitive substeps of replication that could be targeted by current and future therapeutics. A protective replication compartment proved to be essential for sustained RNA replication, balancing translation versus replication and thus effectively limiting RNA amplification. The model predicts that host factors involved in the formation of this compartment determine cellular permissiveness to HCV replication. In gene expression profiling, we identified several key processes potentially determining cellular HCV replication efficiency.
format	article
author	Marco Binder Nurgazy Sulaimanov Diana Clausznitzer Manuel Schulze Christian M Hüber Simon M Lenz Johannes P Schlöder Martin Trippler Ralf Bartenschlager Volker Lohmann Lars Kaderali
author_facet	Marco Binder Nurgazy Sulaimanov Diana Clausznitzer Manuel Schulze Christian M Hüber Simon M Lenz Johannes P Schlöder Martin Trippler Ralf Bartenschlager Volker Lohmann Lars Kaderali
author_sort	Marco Binder
title	Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.
title_short	Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.
title_full	Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.
title_fullStr	Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.
title_full_unstemmed	Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.
title_sort	replication vesicles are load- and choke-points in the hepatitis c virus lifecycle.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e1dc895e827a4dd7b115633d1eeb9a6a
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Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.

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