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

Ziqing Liu, Fang Zhao, Johnny J. He

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Hepatitis C virus (HCV) infection causes the central nervous system(CNS) abnormalities inmore 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 HCVreplication 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 HCVinfection and replication, but HCV interactions with astrocytes and neurons alone might be sufficient to cause CNS dysfunction.

Original languageEnglish
Pages (from-to)278-293
Number of pages16
JournalJournal of NeuroVirology
Volume20
Issue number3
DOIs
Publication statusPublished - Jun 2014

    Fingerprint

Keywords

  • Astrocytes
  • HCV
  • IL-18
  • Neurotoxicity
  • Productive infection
  • Proinflammatory cytokines

Cite this