glycoprotein-e2--hepatitis-c-virus and Epstein-Barr-Virus-Infections

Hepatitis C virus (HCV) E2 protein binds to CD81, which is a component of the B cell co-stimulatory complex. The E2-CD81 interaction leads to B cell proliferation, protein tyrosine phosphorylation and to the hypermutation of immunoglobulin genes. Epidemiological studies have reported a high prevalence of B cell non-Hodgkin lymphoma (NHL) in HCV-positive patients, suggesting a potential association between HCV and Epstein-Barr virus (EBV) in the genesis of B lymphocyte proliferative disorders. In the present study, in order to investigate the association between EBV and HCV in B cells, we created an in vitro EBV-induced B cell transformation model. CD81 was gradually overexpressed during transformation by EBV. B cells isolated from HCV-positive patients grew more rapidly and clumped together earlier than B cells isolated from healthy donors following EBV infection. Pre-stimulation of CD81 expressed by resting B cells with anti-CD81 monoclonal antibody (mAb) or HCV E2 accelerated the generation of lymphoblastoid cell lines (LCLs) by EBV infection. These cells proliferated prominently through the early expression of interleukin-10 and intracellular latent membrane protein (LMP)-l. By contrast, the overexpression of CD81 on EBV-transformed B cells by anti-CD81 mAb or HCV E2 protein induced apoptosis through reactive oxygen species (ROS)-mediated mitochondrial dysfunction. These results suggest that the engagement of CD81 expressed by B cells has differential effects on B cell fate (proliferation or apoptosis) according to EBV infection and the expression level of CD81.

Topics: Adult; Antibodies; Apoptosis; Apoptosis Regulatory Proteins; B-Lymphocytes; Blotting, Western; Cell Proliferation; Cell Transformation, Viral; Cells, Cultured; Epstein-Barr Virus Infections; Female; Hepacivirus; Hepatitis C; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Male; Membrane Potential, Mitochondrial; Microscopy, Confocal; Middle Aged; Protein Binding; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; Tetraspanin 28; Viral Envelope Proteins

To determine the prevalence of hepatitis C virus (HCV) infection in B-cell lymphoma in Japan. HCV infection and type II (monoclonal IgM) cryoglobulinaemia (CG) may be involved in the pathogenesis of low-grade B-cell lymphoma (ML) in southern Europe.. Forty-five (11.3%) of 400 B-cell ML cases were HCV antibody (Ab) positive, which was significantly (P < 0.01) higher than the blood donors (2.5%). Among them, 28 diffuse large B-cell lymphoma (DLBCL) cases were included. In the primary sites, 10 (47.6%) of 21 splenic DLBCL and seven (23.3%) of 30 gastric DLBCL were HCV Ab positive, which were significantly (P < 0.05) higher than the myeloma cases (4.9%). HCV infection was rarely (4.2%) detected in 24 lymphoplasmacytic and salivary gland low-grade B-cell ML cases. Type II CG was detected in one myeloma case (3.5%) of 29 HCV+ B-cell ML. By real-time polymerase chain reaction, HCV RNA was detected in fresh tumour tissues of all 11 B-cell ML cases examined. Lymphoma cells were positive for the envelope HCV non-structural (NS)3 and envelope (E2) proteins in six of eight examined B-cell ML cases.. The rare incidence of type II CG is characteristic of Japanese HCV+ ML patients and may influence the low incidence of low-grade B-cell ML. HCV infection may play a role in lymphomagenesis of splenic and gastric DLBCL.

Topics: Adolescent; Adult; Aged; Child; Comorbidity; Cryoglobulinemia; Epstein-Barr Virus Infections; Female; Genotype; Hepacivirus; Hepatitis B; Hepatitis C; HTLV-I Infections; Humans; Incidence; Japan; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prevalence; RNA, Viral; Viral Envelope Proteins; Viral Nonstructural Proteins