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Cell culture–produced hepatitis C virus does not infect peripheral blood mononuclear cells
Author(s) -
Marukian Svetlana,
Jones Christopher T.,
Andrus Linda,
Evans Matthew J.,
Ritola Kimberly D.,
Charles Edgar D.,
Rice Charles M.,
Dustin Lynn B.
Publication year - 2008
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.22550
Subject(s) - hepatitis c virus , cd81 , virology , peripheral blood mononuclear cell , biology , cell culture , interferon , transfection , virus , hepatitis c , viral replication , hepacivirus , immunology , in vitro , biochemistry , genetics
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‐α. 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. (H EPATOLOGY 2008;48:1843‐1850.)