title: Completion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines.
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.
authors.affiliation: Division of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Frentzen
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hüging
authors.forename: Julia
authors.initials: J
authors.lastname: Bitzegeio
authors.forename: Martina
authors.initials: M
authors.lastname: Friesland
authors.forename: Sibylle
authors.initials: S
authors.lastname: Haid
authors.forename: Juliane
authors.initials: J
authors.lastname: Gentzsch
authors.forename: Markus
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Dirk
authors.initials: D
authors.lastname: Lindemann
authors.forename: Gert
authors.initials: G
authors.lastname: Zimmer
authors.forename: Florian
authors.initials: F
authors.lastname: Zielecki
authors.forename: Friedemann
authors.initials: F
authors.lastname: Weber
authors.forename: Eike
authors.initials: E
authors.lastname: Steinmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Pietschmann
mesh_terms: D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D057809:HEK293 Cells; D006367:HeLa Cells; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D051379:Mice; D023421:Models, Animal; D014162:Transfection; D014779:Virus Replication / Q000235:genetics*
chemical_list: D016898:Interferon-alpha