Completion of Hepatitis C Virus Replication Cycle in Heterokaryons Excludes Dominant Restrictions in Human Non-liver and Mouse Liver Cell Lines

PLoS Pathogens

Kathrin Hüging¹  Juliane Gentzsch¹  Dirk Lindemann¹  Florian Zielecki¹  Eike Steinmann¹  Martina Friesland¹  Gert Zimmer²  Sibylle Haid²  Friedemann Weber²  Markus Hoffmann²  Julia Bitzegeio²  Anne Frentzen²  Thomas Pietschmann⁶ 

[1] a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany;Division of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research;Institute of Virology and Immunoprophylaxis (IVI), Mittelhäusern, Switzerland;Institute of Virology, Carl Gustav Carus Medical Facility, Technical University Dresden, Dresden, Germany;Institute of Virology, Philipps University Marburg, Marburg, Germany;Institute of Virology, University of Veterinary Medicine, Hannover, Germany

关键词: Viral replication;    Cell fusion;    Interferons;    Hepatitis C virus;    Mouse models;    Transfection;    293T cells;    Luciferase;   

DOI  :  10.1371/journal.ppat.1002029

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY