Hepatitis C virus infection of neuroepithelioma cell lines.
OBJECTIVE
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.
Hepatitis C Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham, United Kingdom.
Nicola F
NF
Fletcher
Jian Ping
JP
Yang
Michelle J
MJ
Farquhar
Ke
K
Hu
Christopher
C
Davis
Qiuchen
Q
He
Kimberly
K
Dowd
Stuart C
SC
Ray
Sophie E
SE
Krieger
Johan
J
Neyts
Thomas F
TF
Baumert
Peter
P
Balfe
Jane A
JA
McKeating
Flossie
F
Wong-Staal
D015703:Antigens, CD / Q000502:physiology; D045744:Cell Line, Tumor; D062445:Claudin-1; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000821:virology*; D062793:Occludin; D012367:RNA, Viral / Q000032:analysis; D051122:Scavenger Receptors, Class B / Q000502:physiology; D060225:Tetraspanin 28; D056189:Viral Tropism; D053586:Virus Internalization
D015703:Antigens, CD; C554798:CD81 protein, human; C568108:CLDN1 protein, human; D062445:Claudin-1; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D012367:RNA, Viral; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D060225:Tetraspanin 28