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Hepatitis C virus (HCV) interaction with astrocytes: nonproductive infection and induction of IL-18

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Abstract

Hepatitis C virus (HCV) infection causes the central nervous system (CNS) abnormalities in more than 50 % of chronically infected subjects. However, the underlying mechanisms are largely unknown. In this study, we characterized the HCV interactions with astrocytes, one of the putative HCV target cells in the brain. We demonstrated that primary human astrocytes (PHA) were very inefficiently infected by HCV, either in the cell-free form or through cell–cell contact. We then determined the potential restriction steps of HCV infection and replication in these cells. PHA expressed all known HCV receptors but failed to support HCV entry. HCV IRES-mediated RNA translation was functional in PHA and further enhanced by miR122 expression. Nevertheless, PHA did not support HCV replication regardless of miR122 expression. To our great surprise, we found that HCV exposure induced robust IL-18 expression in PHA and exhibited direct neurotoxicity. Taken together, these results showed that astrocytes did not support productive HCV infection and replication, but HCV interactions with astrocytes and neurons alone might be sufficient to cause CNS dysfunction.

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Acknowledgments

We would like to thank Dr. Charles Rice of Rockefeller University, New York, NY for Huh7.5.1 cells, Dr. Wenzhe Ho of Temple University, Philadelphia, PA for JFH1 virus stock, Dr. Takaji Wakita of National Institute of Infectious Diseases, Japan for JFH1 recombinant plasmid DNA, and Dr. Steve Foung of Stanford University, Stanford, CA for antibodies CBH-2. We would also like to thank Drs. Andy (Qigui) Yu, Randy Brutkiewicz, Cheng Kao, and William Sullivan for their pieces of advice and inputs throughout the study.

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The authors declare that they have no conflict of interest.

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Liu, Z., Zhao, F. & He, J.J. Hepatitis C virus (HCV) interaction with astrocytes: nonproductive infection and induction of IL-18. J. Neurovirol. 20, 278–293 (2014). https://doi.org/10.1007/s13365-014-0245-7

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