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BACKGROUND & AIMS: Hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic syndromes, including central nervous system (CNS) abnormalities. However, it is unclear whether such cognitive abnormalities are a function of systemic disease, impaired hepatic function, or virus infection of the CNS. METHODS: We measured levels of HCV RNA and expression of the viral entry receptor in brain tissue samples from 10 infected individuals (and 3 uninfected individuals, as controls) and human brain microvascular endothelial cells by using quantitative polymerase chain reaction and immunochemical and confocal imaging analyses. HCV pseudoparticles and cell culture-derived HCV were used to study the ability of endothelial cells to support viral entry and replication. RESULTS: Using quantitative polymerase chain reaction, we detected HCV RNA in brain tissue of infected individuals at significantly lower levels than in liver samples. Brain microvascular endothelia and brain endothelial cells expressed all of the recognized HCV entry receptors. Two independently derived brain endothelial cell lines, hCMEC/D3 and HBMEC, supported HCV entry and replication. These processes were inhibited by antibodies against the entry factors CD81, scavenger receptor BI, and claudin-1; by interferon; and by reagents that inhibit NS3 protease and NS5B polymerase. HCV infection promotes endothelial permeability and cellular apoptosis. CONCLUSIONS: Human brain endothelial cells express functional receptors that support HCV entry and replication. Virus infection of the CNS might lead to HCV-associated neuropathologies.

Original publication

DOI

10.1053/j.gastro.2011.11.028

Type

Journal article

Journal

Gastroenterology

Publication Date

03/2012

Volume

142

Pages

634 - 643.e6

Keywords

Adult, Antiviral Agents, Blood-Brain Barrier, Capillary Permeability, Case-Control Studies, Cell Line, Tumor, Endothelial Cells, Female, HEK293 Cells, Hepacivirus, Hepatitis C, Humans, Immunohistochemistry, Liver, Male, Microscopy, Confocal, Microvessels, Middle Aged, RNA, Viral, Real-Time Polymerase Chain Reaction, Receptors, Virus, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Viral Envelope Proteins, Virion, Virus Internalization, Virus Replication