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Hepatitis C virus infection of neuroepithelioma cell lines.

Fletcher, Nicola F and Yang, Jian Ping and Farquhar, Michelle J and Hu, Ke and Davis, Christopher and He, Qiuchen and Dowd, Kimberly and Ray, Stuart C and Krieger, Sophie E and Neyts, Johan and Baumert, Thomas F and Balfe, Peter and McKeating, Jane A and Wong-Staal, Flossie (2010) Hepatitis C virus infection of neuroepithelioma cell lines. Gastroenterology, 139 (4). pp. 1365-74. ISSN 1528-0012

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URL of Published Version: http://dx.doi.org/10.1053/j.gastro.2010.06.008

Identification Number/DOI: 10.1053/j.gastro.2010.06.008

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.

Type of Work:Article
Date:2010 (Publication)
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:Immunity and Infection
Subjects:R Medicine (General)
QR355 Virology
QR180 Immunology
QR Microbiology
Institution:University of Birmingham
Copyright Holders:the AGA Institute
ID Code:459
Refereed:YES
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