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Hepatitis C virus association with peripheral blood B lymphocytes potentiates viral infection of liver-derived hepatoma cells.

Stamataki, Zania and Shannon-Lowe, Claire and Shaw, Jean and Mutimer, David and Rickinson, Alan B and Gordon, John and Adams, David H and Balfe, Peter and McKeating, Jane A (2009) Hepatitis C virus association with peripheral blood B lymphocytes potentiates viral infection of liver-derived hepatoma cells. Blood, 113 (3). pp. 585-93. ISSN 1528-0020

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Identification Number/DOI: 10.1182/blood-2008-05-158824

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.

Type of Work:Article
Date:2009 (Publication)
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:Immunity and Infection
Subjects:R Medicine (General)
QR355 Virology
QR180 Immunology
QR Microbiology
Institution:University of Birmingham
Copyright Holders:American Society of Hematology
ID Code:471
Refereed:YES
Local Holdings:
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