Cell culture-produced hepatitis C virus does not infect peripheral blood mononuclear cells.
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.


CONCLUSIONS
We conclude that multiple blocks prevent blood cells from supporting HCV infection.
Marukian
Svetlana
S
Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
Jones
Christopher T
CT
Andrus
Linda
L
Evans
Matthew J
MJ
Ritola
Kimberly D
KD
Charles
Edgar D
ED
Rice
Charles M
CM
Dustin
Lynn B
LB
D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D062445:Claudin-1; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008565:Membrane Proteins / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D060225:Tetraspanin 28; D014162:Transfection; D014779:Virus Replication / Q000502:physiology*
D015703:Antigens, CD; C554798:CD81 protein, human; C568108:CLDN1 protein, human; D062445:Claudin-1; D008565:Membrane Proteins; D012367:RNA, Viral; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D060225:Tetraspanin 28