Browser does not support script.

The HCV Webserver is run on a Raspberry pi - 2 watts power, $40 complete!

Home > Research > Research activity > Research in the College of Medical and Dental Sciences > Centre for Human Virology > Research > Viral Hepatitis >

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


Zania Stamataki, Claire Shannon-Lowe, Jean Shaw, David Mutimer, Alan Rickinson, John Gordon, David H Adams, Peter Balfe and Jane A McKeating. Blood 113:585-93, 2009.

Pubmed link

back to publications page


Hepatitis C is a complex liver infection that some individuals clear spontaneously, yet most people fail to eliminate the virus and become chronically infected (see diagram 1). The reasons for this are not clear. Our work focuses on the humoral and cellular components of immune responses to HCV, with a special interest in B cells (see diagram 2).
We recently demonstrated in collaboration with Chiron (Novartis) that rodents immunised with vaccines prepared from viral envelope glycoproteins could elicit neutralizing responses (Stamataki, 2007).
To further investigate the role of B lymphocytes in infection, we showed that B cells do not become infected with HCV, yet they can internalize the virus, protect it from neutralizing antibodies. B cells can also deliver HCV to hepatocytes in vitro in a highly infectious form.
Our current experiments address the mechanism of HCV interplay with lymphocytes in the context of the liver.


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 immortalised B cells but fails to establish productive infection. However, B cell-associated virus readily infects hepatoma cells showing an enhanced infectivity compared to 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 trans-infection, supporting a role for these molecules in B cell association with HCV. Stimulation of B cells with CD40 ligand and IL-4 promoted their ability to trans-infect 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.

The process of HCV infection.

Stamataki figure1

The role of B cells in HCV infection.

Stamataki figure2
Stamataki figure3

B cells do not support viral replication but protect the virus from enzymatic degradation and antibody neutralization

Stamataki figure4
Stamataki figure5
Stamataki figure6
Stamataki figure7

B cells do support viral trans-infection

Stamataki figure8
Stamataki figure9

Request a PDF file of this paper