Completion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines.

2.50
Hdl Handle:
http://hdl.handle.net/10033/146355
Title:
Completion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines.
Authors:
Frentzen, Anne; Hüging, Kathrin; Bitzegeio, Julia; Friesland, Martina; Haid, Sibylle; Gentzsch, Juliane; Hoffmann, Markus; Lindemann, Dirk; Zimmer, Gert; Zielecki, Florian; Weber, Friedemann; Steinmann, Eike; Pietschmann, Thomas
Abstract:
Hepatitis C virus (HCV) is hepatotropic and only infects humans and chimpanzees. Consequently, an immunocompetent small animal model is lacking. The restricted tropism of HCV likely reflects specific host factor requirements. We investigated if dominant restriction factors expressed in non-liver or non-human cell lines inhibit HCV propagation thus rendering these cells non-permissive. To this end we explored if HCV completes its replication cycle in heterokaryons between human liver cell lines and non-permissive cell lines from human non-liver or mouse liver origin. Despite functional viral pattern recognition pathways and responsiveness to interferon, virus production was observed in all fused cells and was only ablated when cells were treated with exogenous interferon. These results exclude that constitutive or virus-induced expression of dominant restriction factors prevents propagation of HCV in these cell types, which has important implications for HCV tissue and species tropism. In turn, these data strongly advocate transgenic approaches of crucial human HCV cofactors to establish an immunocompetent small animal model.
Affiliation:
Division of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
Citation:
Completion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines. 2011, 7 (4):e1002029 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Apr-2011
URI:
http://hdl.handle.net/10033/146355
DOI:
10.1371/journal.ppat.1002029
PubMed ID:
21552323
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.authorFrentzen, Anneen
dc.contributor.authorHüging, Kathrinen
dc.contributor.authorBitzegeio, Juliaen
dc.contributor.authorFriesland, Martinaen
dc.contributor.authorHaid, Sibylleen
dc.contributor.authorGentzsch, Julianeen
dc.contributor.authorHoffmann, Markusen
dc.contributor.authorLindemann, Dirken
dc.contributor.authorZimmer, Gerten
dc.contributor.authorZielecki, Florianen
dc.contributor.authorWeber, Friedemannen
dc.contributor.authorSteinmann, Eikeen
dc.contributor.authorPietschmann, Thomasen
dc.date.accessioned2011-10-21T13:45:31Z-
dc.date.available2011-10-21T13:45:31Z-
dc.date.issued2011-04-
dc.identifier.citationCompletion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines. 2011, 7 (4):e1002029 PLoS Pathog.en
dc.identifier.issn1553-7374-
dc.identifier.pmid21552323-
dc.identifier.doi10.1371/journal.ppat.1002029-
dc.identifier.urihttp://hdl.handle.net/10033/146355-
dc.description.abstractHepatitis C virus (HCV) is hepatotropic and only infects humans and chimpanzees. Consequently, an immunocompetent small animal model is lacking. The restricted tropism of HCV likely reflects specific host factor requirements. We investigated if dominant restriction factors expressed in non-liver or non-human cell lines inhibit HCV propagation thus rendering these cells non-permissive. To this end we explored if HCV completes its replication cycle in heterokaryons between human liver cell lines and non-permissive cell lines from human non-liver or mouse liver origin. Despite functional viral pattern recognition pathways and responsiveness to interferon, virus production was observed in all fused cells and was only ablated when cells were treated with exogenous interferon. These results exclude that constitutive or virus-induced expression of dominant restriction factors prevents propagation of HCV in these cell types, which has important implications for HCV tissue and species tropism. In turn, these data strongly advocate transgenic approaches of crucial human HCV cofactors to establish an immunocompetent small animal model.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshCell Fusionen
dc.subject.meshCell Lineen
dc.subject.meshHEK293 Cellsen
dc.subject.meshHela Cellsen
dc.subject.meshHepacivirusen
dc.subject.meshHumansen
dc.subject.meshInterferon-alphaen
dc.subject.meshMiceen
dc.subject.meshModels, Animalen
dc.subject.meshTransfectionen
dc.subject.meshVirus Replicationen
dc.titleCompletion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines.en
dc.typeArticleen
dc.contributor.departmentDivision of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.en
dc.identifier.journalPLoS pathogensen

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