In-vitro infection of chronic lymphocytic leukemia cells by Epstein-Barr virus (EBV).
We sought to determine the potential of infecting lymphoid cells from patients with chronic leukemia (CLL) with Epstein-Barr virus (EBV) by testing for EBV receptors (EBVR) by flow cytometry, assessing for infectability of these cells by culturing with B95-8-derived virus, and staining for EB nuclear-associated antigens (EBNA) at various times post-infection. EBVR were present on 54-91% of lymphoid cells in seven cases of CLL and on 46% of prolymphocytic leukemia cells. Dynamic changes regarding EBNA positivity, morphology, and viability occurred post-infection with the virus. On day 2 only a few EBNA-positive lymphoblasts were observed. On days 11-21 positivity increased from 2 to 34% of cells. Simultaneously, the viable cell number declined to approximately 1/10th of original number. A significant proportion of the EBNA-positive cells corresponded to the original CLL cells. In 3 of 7 cases of CLL a Pan T-cell phenotype was demonstrated by Leu-1 monoclonal antibody testing. The infected cells did not react with two monoclonal antibodies, EBV-CS 1 and 4, which react with B-cell lymphoblastoid cell lines (B-LCL). Moreover, the B-LCL derived at 1-2 months post-infection of CLL cells did not express the Leu-1 antigen, but expressed EBV-CS 1 or 4 defined antigens. In the prolymphocytic leukemia, 64% of the cells showed EBNA positivity on day 7 and giant cells with huge round or multiple nuclei appeared which were EBNA-positive. CLL and prolymphocytic leukemia cells can be infected as demonstrated by EBNA-positivity. This infection does not lead to immediate transformation, but evokes lymphoblast and multinucleated giant cell production prior to the death of cells.
D000368:Aged; D002472:Cell Transformation, Viral; D029043:Ebolavirus / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007945:Leukemia, Lymphoid / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D011951:Receptors, Complement / Q000032:analysis; D011991:Receptors, Virus / Q000032:analysis; D012209:Rhabdoviridae / Q000235:genetics*
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D011951:Receptors, Complement; D011991:Receptors, Virus