Document Detail


Persistent expression of the full genome of hepatitis C virus in B cells induces spontaneous development of B-cell lymphomas in vivo.
MedLine Citation:
PMID:  20733156     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Extrahepatic 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.
Authors:
Yuri Kasama; Satoshi Sekiguchi; Makoto Saito; Kousuke Tanaka; Masaaki Satoh; Kazuhiko Kuwahara; Nobuo Sakaguchi; Motohiro Takeya; Yoichi Hiasa; Michinori Kohara; Kyoko Tsukiyama-Kohara
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-23
Journal Detail:
Title:  Blood     Volume:  116     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-03     Completed Date:  2011-01-06     Revised Date:  2011-07-22    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4926-33     Citation Subset:  AIM; IM    
Affiliation:
Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Transformation, Neoplastic / genetics*
Cell Transformation, Viral / genetics
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Genes, Viral
Hepacivirus / genetics*
Immunohistochemistry
Interleukin-2 Receptor alpha Subunit / biosynthesis
Lymphoma, Large B-Cell, Diffuse / pathology,  virology*
Male
Mice
Mice, Transgenic
RNA, Messenger / analysis
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Interleukin-2 Receptor alpha Subunit; 0/RNA, Messenger
Comments/Corrections
Erratum In:
Blood. 2011 May 26;117(21):5782-3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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