Hepatitis C virus infection of neuroepithelioma cell lines.

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.

• Authors: Nicola F Fletcher, Jian Ping Yang, Michelle J Farquhar, Ke Hu, Christopher Davis, Qiuchen He, Kimberly Dowd, Stuart C Ray, Sophie E Krieger, Johan Neyts, Thomas F Baumert, Peter Balfe, Jane A McKeating, Flossie Wong-Staal
• Journal: Gastroenterology (Gastroenterology) Vol. 139 Issue 4 Pg. 1365-74 (Oct 2010) ISSN: 1528-0012 [Electronic] United States
• PMID: 20538002 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD
• CD81 protein, human
• CLDN1 protein, human
• Claudin-1
• Membrane Proteins
• OCLN protein, human
• Occludin
• RNA, Viral
• SCARB1 protein, human
• Scavenger Receptors, Class B
• Tetraspanin 28

Topics

• Antigens, CD (physiology)
• Cell Line, Tumor
• Claudin-1
• Hepacivirus (physiology)
• Humans
• Membrane Proteins (physiology)
• Neuroectodermal Tumors, Primitive, Peripheral (virology)
• Occludin
• RNA, Viral (analysis)
• Scavenger Receptors, Class B (physiology)
• Tetraspanin 28
• Viral Tropism
• Virus Internalization