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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Anne Frentzen - , Division of Experimental Virology (Autor:in)
  • Kathrin Hüging - (Autor:in)
  • Julia Bitzegeio - (Autor:in)
  • Martina Friesland - (Autor:in)
  • Sibylle Haid - (Autor:in)
  • Juliane Gentzsch - (Autor:in)
  • Markus Hoffmann - (Autor:in)
  • Dirk Lindemann - , Institut für Medizinische Mikrobiologie und Virologie (Autor:in)
  • Gert Zimmer - (Autor:in)
  • Florian Zielecki - (Autor:in)
  • Friedemann Weber - (Autor:in)
  • Eike Steinmann - (Autor:in)
  • Thomas Pietschmann - (Autor:in)

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)e1002029
FachzeitschriftPLOS pathogens
Jahrgang7
Ausgabenummer4
PublikationsstatusVeröffentlicht - Apr. 2011
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC3084199
ORCID /0000-0002-0320-4223/work/150885072
Scopus 79955752803

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Animals, Cell Fusion, Cell Line, HEK293 Cells, HeLa Cells, Hepacivirus/physiology, Humans, Interferon-alpha/pharmacology, Mice, Models, Animal, Transfection, Virus Replication/genetics