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Low cell dosage of lymphoblastoid human cell lines EBV + is associated to chronic hepatitis in a minority of inoculated nu/nu mice
Author(s) -
Bertolini Luisa,
Iacovacci Silvia,
Bosman Cesare,
Carloni Guido,
Monaco Vincenzo,
Bangrazi Caterina,
Serafino Annalucia,
Gualandi Giampiero,
Prantera Giorgio,
Fruscalzo Alberto
Publication year - 2002
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.2113
Subject(s) - virology , biology , lymphoblast , cell culture , lymphoproliferative disorders , epstein–barr virus , lymphocyte , b cell , lymphoproliferative response , virus , in vitro , microbiology and biotechnology , immunology , lymphoma , antibody , peripheral blood mononuclear cell , genetics , biochemistry
It has been suggested that an atypical course of primary infection by EBV and the reactivation of EBV infection in transplanted patients may induce hepatitis. We explored the possibility to dissect the infectious activity from the ability to promote B lymphocyte proliferation in vivo by injecting in nu/nu mice a low number (2 × 10 6 –0.05 × 10 6 ) of cells from CE a normal human bone marrow–derived B cell line. This line carries an endogenous EBV in episomal and linear forms. Twenty nu/nu mice were inoculated subcutaneously with the B cell line CE and a matched group with the cell line RAG obtained by EBV in vitro infection of normal human peripheral blood. The mice injected with the CE line did not develop a lymphoproliferative disease, but 5 of them displayed typical histopathological lesions of chronic hepatitis without involvement of other organs. Similar results were obtained in 2 out of 20 animals in the RAG group. A close association between liver lesions and a previous EBV infection, by putative circulating B lymphoblastoid cells releasing their EBV, was established by PCR and by in situ hybridization with BamHI “W” DNA probe. This latter probe detected the presence of about 15% of positive cells only in affected livers. In addition, the rare detection in some hepatocytes of “A” type Cowdry bodies would suggest the occurrence of continuous EBV replication although at a very low level. These data show that we succeeded in dissecting the infectious from the proliferative activity of the endogenous EBV carrier CE cell line. This provides in addition a promising model for chronic EBV‐associated hepatitis. J. Med. Virol. 66:70–81, 2002. © 2002 Wiley‐Liss, Inc.