2.50
Hdl Handle:
http://hdl.handle.net/10033/293005
Title:
Hepatitis C Virus p7 is Critical for Capsid Assembly and Envelopment.
Authors:
Gentzsch, Juliane; Brohm, Christiane; Steinmann, Eike; Friesland, Martina; Menzel, Nicolas; Vieyres, Gabrielle; Perin, Paula Monteiro; Frentzen, Anne; Kaderali, Lars; Pietschmann, Thomas
Abstract:
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.
Affiliation:
Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Citation:
Hepatitis C Virus p7 is Critical for Capsid Assembly and Envelopment. 2013, 9 (5):e1003355 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
May-2013
URI:
http://hdl.handle.net/10033/293005
DOI:
10.1371/journal.ppat.1003355
PubMed ID:
23658526
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the department experimental Virology([TC]EVIR)

Full metadata record

DC FieldValue Language
dc.contributor.authorGentzsch, Julianeen_GB
dc.contributor.authorBrohm, Christianeen_GB
dc.contributor.authorSteinmann, Eikeen_GB
dc.contributor.authorFriesland, Martinaen_GB
dc.contributor.authorMenzel, Nicolasen_GB
dc.contributor.authorVieyres, Gabrielleen_GB
dc.contributor.authorPerin, Paula Monteiroen_GB
dc.contributor.authorFrentzen, Anneen_GB
dc.contributor.authorKaderali, Larsen_GB
dc.contributor.authorPietschmann, Thomasen_GB
dc.date.accessioned2013-05-29T10:36:29Z-
dc.date.available2013-05-29T10:36:29Z-
dc.date.issued2013-05-
dc.identifier.citationHepatitis C Virus p7 is Critical for Capsid Assembly and Envelopment. 2013, 9 (5):e1003355 PLoS Pathog.en_GB
dc.identifier.issn1553-7374-
dc.identifier.pmid23658526-
dc.identifier.doi10.1371/journal.ppat.1003355-
dc.identifier.urihttp://hdl.handle.net/10033/293005-
dc.description.abstractHepatitis 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen_GB
dc.titleHepatitis C Virus p7 is Critical for Capsid Assembly and Envelopment.en
dc.typeArticleen
dc.contributor.departmentInstitute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.en_GB
dc.identifier.journalPLoS pathogensen_GB

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.