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UNLABELLED: Hepatitis C virus (HCV) replicates primarily in the liver, but HCV RNA has been observed in association with other tissues and cells including B and T lymphocytes, monocytes, and dendritic cells. We have taken advantage of a recently described, robust system that fully recapitulates HCV entry, replication and virus production in vitro to re-examine the issue of HCV infection of blood cell subsets. The HCV replicase inhibitor 2'C-methyl adenosine was used to distinguish HCV RNA replication from RNA persistence. Whereas cell culture-grown HCV replicated in Huh-7.5 hepatoma cells, no HCV replication was detected in B or T lymphocytes, monocytes, macrophages, or dendritic cells from healthy donors. No blood cell subset tested expressed significant levels of Claudin-1, a tight junction protein needed for HCV infection of Huh-7.5 cells. A B cell line expressing high levels of Claudin-1, CD81, and scavenger receptor BI remained resistant to HCV pseudoparticle infection. We bypassed the block in HCV entry by transfecting HCV RNA into blood cell subsets. Transfected RNA was not detectably translated and induced high levels of interferon-alpha. Supernatants from HCV RNA-transfected macrophages inhibited HCV replication in Huh-7.5 cells. CONCLUSION: We conclude that multiple blocks prevent blood cells from supporting HCV infection.

Original publication

DOI

10.1002/hep.22550

Type

Journal article

Journal

Hepatology

Publication Date

12/2008

Volume

48

Pages

1843 - 1850

Keywords

Antigens, CD, B-Lymphocytes, Carcinoma, Hepatocellular, Cell Line, Cell Line, Tumor, Cells, Cultured, Claudin-1, Dendritic Cells, Hepacivirus, Humans, Leukocytes, Mononuclear, Liver Neoplasms, Membrane Proteins, RNA, Viral, Scavenger Receptors, Class B, Tetraspanin 28, Transfection, Virus Replication