Hepatitis C virus infection of neuroepithelioma cell lines

Nicola F. Fletcher, Jian Ping Yang, Michelle J. Farquhar, Ke Hu, Christopher Davis, Qiuchen He, Kimberly Dowd, Stuart Campbell Ray, Sophie E. Krieger, Johan Neyts, Thomas F. Baumert, Peter Balfe, Jane A. McKeating, Flossie Wongstaal

Research output: Contribution to journalArticle

Abstract

Background & Aims: Hepatitis C virus (HCV) establishes chronic infections in 3% of the world's population. Infection leads to progressive liver disease; hepatocytes are the major site of viral replication in vivo. However, chronic infection is associated with a variety of extrahepatic syndromes, including central nervous system (CNS) abnormalities. We therefore screened a series of neural and brain-derived cell lines for their ability to support HCV entry and replication. Methods: We used a panel of neural-derived cell lines, HCV pseudoparticles (HCVpp), and an infectious, HCV JFH-1 cell-culture system (HCVcc) to assess viral tropism. Results: Two independently derived neuroepithelioma cell lines (SK-N-MC and SK-PN-DW) permitted HCVpp entry. In contrast, several neuroblastoma, glioma, and astrocytoma cell lines were refractory to HCVpp infection. HCVcc infected the neuroepithelioma cell lines and established a productive infection. Permissive neuroepithelioma cells expressed CD81, scavenger receptor BI (SR-BI), and the tight junction proteins Claudin-1 (CLDN1) and occludin, whereas nonpermissive neural cell lines lacked CLDN1 and, in some cases, SR-BI. HCVpp infection of the neuroepithelioma cells was neutralized by antibodies to CD81, SR-BI, CLDN1, and HCV E2. Furthermore, anti-CD81, interferon, and the anti-NS3 protease inhibitor VX-950 significantly reduced HCVcc infection of neuroepithelioma and hepatoma cells. Conclusions: Neuroepithelioma-derived cell lines express functional receptors that support HCV entry at levels comparable to those of hepatoma cells. HCV infection in vitro is not restricted to hepatic-derived cells, so HCV might infect cells of the CNS in vivo.

Original languageEnglish (US)
JournalGastroenterology
Volume139
Issue number4
DOIs
StatePublished - Oct 2010

Fingerprint

Virus Diseases
Hepacivirus
Cell Line
Claudin-1
Scavenger Receptors
Infection
Virus Internalization
Cell Culture Techniques
Hepatocytes
Hepatocellular Carcinoma
Hepatovirus
Viral Tropism
Central Nervous System
Zonula Occludens-1 Protein
Nervous System Malformations
Occludin
Astrocytoma
Virus Replication
Protease Inhibitors
Neuroblastoma

Keywords

  • Brain
  • Huh-7
  • Neurotropism
  • OCLN
  • Replicon
  • Therapy
  • VX-950

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

Fletcher, N. F., Yang, J. P., Farquhar, M. J., Hu, K., Davis, C., He, Q., ... Wongstaal, F. (2010). Hepatitis C virus infection of neuroepithelioma cell lines. Gastroenterology, 139(4). https://doi.org/10.1053/j.gastro.2010.06.008

Hepatitis C virus infection of neuroepithelioma cell lines. / Fletcher, Nicola F.; Yang, Jian Ping; Farquhar, Michelle J.; Hu, Ke; Davis, Christopher; He, Qiuchen; Dowd, Kimberly; Ray, Stuart Campbell; Krieger, Sophie E.; Neyts, Johan; Baumert, Thomas F.; Balfe, Peter; McKeating, Jane A.; Wongstaal, Flossie.

In: Gastroenterology, Vol. 139, No. 4, 10.2010.

Research output: Contribution to journalArticle

Fletcher, NF, Yang, JP, Farquhar, MJ, Hu, K, Davis, C, He, Q, Dowd, K, Ray, SC, Krieger, SE, Neyts, J, Baumert, TF, Balfe, P, McKeating, JA & Wongstaal, F 2010, 'Hepatitis C virus infection of neuroepithelioma cell lines', Gastroenterology, vol. 139, no. 4. https://doi.org/10.1053/j.gastro.2010.06.008
Fletcher NF, Yang JP, Farquhar MJ, Hu K, Davis C, He Q et al. Hepatitis C virus infection of neuroepithelioma cell lines. Gastroenterology. 2010 Oct;139(4). https://doi.org/10.1053/j.gastro.2010.06.008
Fletcher, Nicola F. ; Yang, Jian Ping ; Farquhar, Michelle J. ; Hu, Ke ; Davis, Christopher ; He, Qiuchen ; Dowd, Kimberly ; Ray, Stuart Campbell ; Krieger, Sophie E. ; Neyts, Johan ; Baumert, Thomas F. ; Balfe, Peter ; McKeating, Jane A. ; Wongstaal, Flossie. / Hepatitis C virus infection of neuroepithelioma cell lines. In: Gastroenterology. 2010 ; Vol. 139, No. 4.
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AU - He, Qiuchen

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AU - Ray, Stuart Campbell

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