title: Low cell dosage of lymphoblastoid human cell lines EBV(+) is associated to chronic hepatitis in a minority of inoculated Nu/Nu mice.
abstract: 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 x 10(6)-0.05 x 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.
authors.affiliation: Istituto di Biologia Cellulare Consiglio Nazionale delle Ricerche (CNR), Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Bertolini
authors.forename: Silvia
authors.initials: S
authors.lastname: Iacovacci
authors.forename: Cesare
authors.initials: C
authors.lastname: Bosman
authors.forename: Guido
authors.initials: G
authors.lastname: Carloni
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Monaco
authors.forename: Caterina
authors.initials: C
authors.lastname: Bangrazi
authors.forename: Annalucia
authors.initials: A
authors.lastname: Serafino
authors.forename: Giampiero
authors.initials: G
authors.lastname: Gualandi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Prantera
authors.forename: Alberto
authors.initials: A
authors.lastname: Fruscalzo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000637:transplantation* / Q000821:virology*; D002461:Cell Line, Transformed; D004279:DNA, Viral / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000821:virology; D006521:Hepatitis, Chronic / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000302:isolation & purification* / Q000472:pathogenicity; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000473:pathology / Q000821:virology; D017710:Lymphocyte Transfusion; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous
chemical_list: D004279:DNA, Viral