hepatitis c Virus p7 is critical for capsid assembly and envelopment.

Hepatitis C virus (HCV) p7 is a membrane-associated ion channel protein crucial for virus production. To analyze how p7 contributes to this process, we dissected HCV morphogenesis into sub-steps including recruitment of HCV core to lipid droplets (LD), virus capsid assembly, unloading of core protei...

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Autores principales:	Juliane Gentzsch, Christiane Brohm, Eike Steinmann, Martina Friesland, Nicolas Menzel, Gabrielle Vieyres, Paula Monteiro Perin, Anne Frentzen, Lars Kaderali, Thomas Pietschmann
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/ae9afdda1fd142e7b3c7df348746eb57
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spelling	oai:doaj.org-article:ae9afdda1fd142e7b3c7df348746eb572021-11-18T06:05:41Zhepatitis c Virus p7 is critical for capsid assembly and envelopment.1553-73661553-737410.1371/journal.ppat.1003355https://doaj.org/article/ae9afdda1fd142e7b3c7df348746eb572013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23658526/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Hepatitis C virus (HCV) p7 is a membrane-associated ion channel protein crucial for virus production. To analyze how p7 contributes to this process, we dissected HCV morphogenesis into sub-steps including recruitment of HCV core to lipid droplets (LD), virus capsid assembly, unloading of core protein from LDs and subsequent membrane envelopment of capsids. Interestingly, we observed accumulation of slowly sedimenting capsid-like structures lacking the viral envelope in cells transfected with HCV p7 mutant genomes which possess a defect in virion production. Concomitantly, core protein was enriched at the surface of LDs. This indicates a defect in core/capsid unloading from LDs and subsequent membrane envelopment rather than defective trafficking of core to this cellular organelle. Protease and ribonuclease digestion protection assays, rate zonal centrifugation and native, two dimensional gel electrophoresis revealed increased amounts of high-order, non-enveloped core protein complexes unable to protect viral RNA in cells transfected with p7 mutant genomes. These results suggest accumulation of capsid assembly intermediates that had not yet completely incorporated viral RNA in the absence of functional p7. Thus, functional p7 is necessary for the final steps of capsid assembly as well as for capsid envelopment. These results support a model where capsid assembly is linked with membrane envelopment of nascent RNA-containing core protein multimers, a process coordinated by p7. In summary, we provide novel insights into the sequence of HCV assembly events and essential functions of p7.Juliane GentzschChristiane BrohmEike SteinmannMartina FrieslandNicolas MenzelGabrielle VieyresPaula Monteiro PerinAnne FrentzenLars KaderaliThomas PietschmannPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 5, p e1003355 (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 Juliane Gentzsch Christiane Brohm Eike Steinmann Martina Friesland Nicolas Menzel Gabrielle Vieyres Paula Monteiro Perin Anne Frentzen Lars Kaderali Thomas Pietschmann hepatitis c Virus p7 is critical for capsid assembly and envelopment.
description	Hepatitis C virus (HCV) p7 is a membrane-associated ion channel protein crucial for virus production. To analyze how p7 contributes to this process, we dissected HCV morphogenesis into sub-steps including recruitment of HCV core to lipid droplets (LD), virus capsid assembly, unloading of core protein from LDs and subsequent membrane envelopment of capsids. Interestingly, we observed accumulation of slowly sedimenting capsid-like structures lacking the viral envelope in cells transfected with HCV p7 mutant genomes which possess a defect in virion production. Concomitantly, core protein was enriched at the surface of LDs. This indicates a defect in core/capsid unloading from LDs and subsequent membrane envelopment rather than defective trafficking of core to this cellular organelle. Protease and ribonuclease digestion protection assays, rate zonal centrifugation and native, two dimensional gel electrophoresis revealed increased amounts of high-order, non-enveloped core protein complexes unable to protect viral RNA in cells transfected with p7 mutant genomes. These results suggest accumulation of capsid assembly intermediates that had not yet completely incorporated viral RNA in the absence of functional p7. Thus, functional p7 is necessary for the final steps of capsid assembly as well as for capsid envelopment. These results support a model where capsid assembly is linked with membrane envelopment of nascent RNA-containing core protein multimers, a process coordinated by p7. In summary, we provide novel insights into the sequence of HCV assembly events and essential functions of p7.
format	article
author	Juliane Gentzsch Christiane Brohm Eike Steinmann Martina Friesland Nicolas Menzel Gabrielle Vieyres Paula Monteiro Perin Anne Frentzen Lars Kaderali Thomas Pietschmann
author_facet	Juliane Gentzsch Christiane Brohm Eike Steinmann Martina Friesland Nicolas Menzel Gabrielle Vieyres Paula Monteiro Perin Anne Frentzen Lars Kaderali Thomas Pietschmann
author_sort	Juliane Gentzsch
title	hepatitis c Virus p7 is critical for capsid assembly and envelopment.
title_short	hepatitis c Virus p7 is critical for capsid assembly and envelopment.
title_full	hepatitis c Virus p7 is critical for capsid assembly and envelopment.
title_fullStr	hepatitis c Virus p7 is critical for capsid assembly and envelopment.
title_full_unstemmed	hepatitis c Virus p7 is critical for capsid assembly and envelopment.
title_sort	hepatitis c virus p7 is critical for capsid assembly and envelopment.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/ae9afdda1fd142e7b3c7df348746eb57
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hepatitis c Virus p7 is critical for capsid assembly and envelopment.

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