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Completion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines.
Frentzen, Anne Hüging, Kathrin Bitzegeio, Julia Friesland, Martina Haid, Sibylle Gentzsch, Juliane Hoffmann, Markus Lindemann, Dirk Zimmer, Gert Zielecki, Florian
Frentzen, Anne
Hüging, Kathrin
Bitzegeio, Julia
Friesland, Martina
Haid, Sibylle
Gentzsch, Juliane
Hoffmann, Markus
Lindemann, Dirk
Zimmer, Gert
Zielecki, Florian
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2011-04
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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.
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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.
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en
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1553-7374