Hepatitis C virus association with peripheral blood B lymphocytes potentiates viral infection of liver-derived hepatoma cells.
Hepatitis C virus (HCV) primarily replicates within the liver, leading to hepatitis, fibrosis, and hepatocellular carcinoma. Infection is also associated with B-cell abnormalities, suggesting an association of the virus with B cells. The infectious JFH-1 strain of HCV can bind primary and immortalized B cells but fails to establish productive infection. However, B cell-associated virus readily infects hepatoma cells, showing an enhanced infectivity compared with extracellular virus. B cells express the viral receptors CD81, SR-BI, and the C-type lectins DC-SIGN and L-SIGN. Antibodies specific for SR-BI and DC-SIGN/L-SIGN reduced B-cell transinfection, supporting a role for these molecules in B-cell association with HCV. Stimulation of B cells with CD40 ligand and interleukin-4 promoted their ability to transinfect hepatoma cells. B cell-associated virus is resistant to trypsin proteolysis and HCV-specific neutralizing antibodies, consistent with particle internalization. HCV promoted the adhesion of primary B cells to Huh-7 hepatomas, providing a mechanism for B-cell retention in the infected liver. In summary, B cells may provide a vehicle for HCV to persist and transmit to the liver.
Hepatitis C Virus Research Group, Division of Immunity and Infection, Institute for Cancer Studies, UK
Zania
Z
Stamataki
Claire
C
Shannon-Lowe
Jean
J
Shaw
David
D
Mutimer
Alan B
AB
Rickinson
John
J
Gordon
David H
DH
Adams
Peter
P
Balfe
Jane A
JA
McKeating
D000818:Animals; D001402:B-Lymphocytes / Q000821:virology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D005434:Flow Cytometry; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000635:transmission*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D011991:Receptors, Virus / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011991:Receptors, Virus