scholarly journals Hepatitis C Virus E2-CD81 Interaction Induces Hypermutation of the Immunoglobulin Gene in B Cells

2005 ◽  
Vol 79 (13) ◽  
pp. 8079-8089 ◽  
Author(s):  
Keigo Machida ◽  
Kevin T.-H. Cheng ◽  
Nicole Pavio ◽  
Vicky M.-H. Sung ◽  
Michael M. C. Lai
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cells ◽  
B Cell ◽  
B Cell Lymphoma ◽  
Immunoglobulin Gene ◽  
Dna Breaks ◽  
Necrosis Factor Alpha ◽  
Double Strand Dna Breaks ◽  
Double Strand Dna

ABSTRACT Hepatitis C virus (HCV) is one of the leading causes of chronic liver diseases and B-lymphocyte proliferative disorders, including mixed cryoglobulinemia and B-cell lymphoma. It has been suggested that HCV infects human cells through the interaction of its envelope glycoprotein E2 with a tetraspanin molecule CD81, the putative viral receptor. Here, we show that the engagement of B cells by purified E2 induced double-strand DNA breaks specifically in the variable region of immunoglobulin (VH ) gene locus, leading to hypermutation in the VH genes of B cells. Other gene loci were not affected. Preincubation with the anti-CD81 monoclonal antibody blocked this effect. E2-CD81 interaction on B cells triggered the enhanced expression of activation-induced cytidine deaminase (AID) and also stimulated the production of tumor necrosis factor alpha. Knockdown of AID by the specific small interfering RNA blocked the E2-induced double-strand DNA breaks and hypermutation of the VH gene. These findings suggest that HCV infection, through E2-CD81 interaction, may modulate host's innate or adaptive immune response by activation of AID and hypermutation of immunoglobulin gene in B cells, leading to HCV-associated B-cell lymphoproliferative diseases.

scholarly journals Persistent expression of the full genome of hepatitis C virus in B cells induces spontaneous development of B-cell lymphomas in vivo

Blood ◽  
2010 ◽  
Vol 116 (23) ◽  
pp. 4926-4933 ◽  
Author(s):  
Yuri Kasama ◽  
Satoshi Sekiguchi ◽  
Makoto Saito ◽  
Kousuke Tanaka ◽  
Masaaki Satoh ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hcv Infection ◽  
Mouse Serum ◽  
B Cell Lymphomas ◽  
Α Subunit

AbstractExtrahepatic manifestations of hepatitis C virus (HCV) infection occur in 40%-70% of HCV-infected patients. B-cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with HCV infection. The mechanism by which HCV infection of B cells leads to lymphoma remains unclear. Here we established HCV transgenic mice that express the full HCV genome in B cells (RzCD19Cre mice) and observed a 25.0% incidence of diffuse large B-cell non-Hodgkin lymphomas (22.2% in males and 29.6% in females) within 600 days after birth. Expression levels of aspartate aminotransferase and alanine aminotransferase, as well as 32 different cytokines, chemokines and growth factors, were examined. The incidence of B-cell lymphoma was significantly correlated with only the level of soluble interleukin-2 receptor α subunit (sIL-2Rα) in RzCD19Cre mouse serum. All RzCD19Cre mice with substantially elevated serum sIL-2Rα levels (> 1000 pg/mL) developed B-cell lymphomas. Moreover, compared with tissues from control animals, the B-cell lymphoma tissues of RzCD19Cre mice expressed significantly higher levels of IL-2Rα. We show that the expression of HCV in B cells promotes non-Hodgkin–type diffuse B-cell lymphoma, and therefore, the RzCD19Cre mouse is a powerful model to study the mechanisms related to the development of HCV-associated B-cell lymphoma.

Primary hepatic or splenic diffuse large B-cell lymphoma and hepatitis C virus infection: a non-fortuitous association?

2000 ◽  
Vol 79 (9) ◽  
pp. 530-532 ◽  
Author(s):  
I. Genvresse ◽  
E. Späth-Schwalbe ◽  
H. Meisel ◽  
O. Kaufmann ◽  
D. H. Krüger ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hepatitis C Virus Infection ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Concomitant Treatment of Hepatitis C Virus and Diffuse Large B-Cell Lymphoma with Direct-Acting Antivirals in HIV Coinfection: A Case Report

2019 ◽  
Vol 18 ◽  
pp. 232595821882206
Author(s):  
Alyssa Gallipani ◽  
Agnes Cha ◽  
Leonard Berkowitz ◽  
Anjali Bakshi
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Concomitant Treatment ◽  
Direct Acting Antivirals ◽  
Large B Cell Lymphoma ◽  
Direct Acting ◽  
Large B Cell

This report describes a case of concomitant treatment of advanced diffuse large B-cell lymphoma with chemoimmunotherapy along with direct-acting antivirals for hepatitis C virus in a patient coinfected with HIV. The patient tolerated gemcitabine, dexamethasone, cisplatin, and rituximab and achieved sustained virologic response after treatment with ledipasvir/sofosbuvir.

Direct-acting antivirals in relapsed or refractory hepatitis C virus-associated diffuse large B-cell lymphoma

2020 ◽  
Vol 61 (9) ◽  
pp. 2122-2128 ◽  
Author(s):  
Michele Merli ◽  
Irene Defrancesco ◽  
Carlo Visco ◽  
Caroline Besson ◽  
Alice Di Rocco ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Direct Acting Antivirals ◽  
Large B Cell Lymphoma ◽  
Direct Acting ◽  
Large B Cell

Prevalence of hepatitis C virus infection in cases of B-cell lymphoma in Japan

2006 ◽  
Vol 48 (2) ◽  
pp. 189-198 ◽  
Author(s):  
M Takeshita ◽  
H Sakai ◽  
S Okamura ◽  
K Higaki ◽  
Y Oshiro ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hepatitis C Virus Infection

scholarly journals Antibody Production and In Vitro Behavior of CD27-Defined B-Cell Subsets: Persistent Hepatitis C Virus Infection Changes the Rules

2006 ◽  
Vol 80 (8) ◽  
pp. 3923-3934 ◽  
Author(s):  
Vito Racanelli ◽  
Maria Antonia Frassanito ◽  
Patrizia Leone ◽  
Maria Galiano ◽  
Valli De Re ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Feedback Inhibition ◽  
Cell Subset ◽  
Functional Program ◽  
Cell Functions

ABSTRACT There is growing interest in the tendency of B cells to change their functional program in response to overwhelming antigen loading, perhaps by regulating specific parameters, such as efficiency of activation, proliferation rate, differentiation to antibody-secreting cells (ASC), and rate of cell death in culture. We show that individuals persistently infected with hepatitis C virus (HCV) carry high levels of circulating immunoglobulin G (IgG) and IgG-secreting cells (IgG-ASC). Thus, generalized polyclonal activation of B-cell functions may be supposed. While IgGs include virus-related and unrelated antibodies, IgG-ASC do not include HCV-specific plasma cells. Despite signs of widespread activation, B cells do not accumulate and memory B cells seem to be reduced in the blood of HCV-infected individuals. This apparent discrepancy may reflect the unconventional activation kinetics and functional responsiveness of the CD27+ B-cell subset in vitro. Following stimulation with T-cell-derived signals in the absence of B-cell receptor (BCR) engagement, CD27+ B cells do not expand but rapidly differentiate to secrete Ig and then undergo apoptosis. We propose that their enhanced sensitivity to BCR-independent noncognate T-cell help maintains a constant level of nonspecific serum antibodies and ASC and serves as a backup mechanism of feedback inhibition to prevent exaggerated B-cell responses that could be the cause of significant immunopathology.

scholarly journals Antiviral therapy improves overall survival in hepatitis C virus-infected patients who develop diffuse large B-cell lymphoma

2016 ◽  
Vol 139 (11) ◽  
pp. 2519-2528 ◽  
Author(s):  
Jeff Hosry ◽  
Parag Mahale ◽  
Francesco Turturro ◽  
Roberto N. Miranda ◽  
Minas P. Economides ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Antiviral Therapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell
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