EPSTEIN-BARR VIRUS INTERACTIONS WITH HUMAN LYMPHOCYTE SUBPOPULATIONS - VIRUS ADSORPTION, KINETICS OF EXPRESSION OF EPSTEIN-BARR VIRUS-ASSOCIATED NUCLEAR ANTIGEN, AND LYMPHOCYTE-TRANSFORMATION

To further understand Epstein-Barr virus (EBV)-lymphocyte interactions, a chain of events was investigated including EBV binding to human lymphocyte subpopulations, the earliest appearance of EBV-determined nuclear antigen (EBNA) in the lymphocytes after EBV infection and establishment of continuous lymphoblastoid cell lines (LCL) by infecting with EBV different types of lymphocyte preparations from the same and from different donors. Direct memebrane immunofluorescence, revealed that only a small fraction of human peripheral blood and cord blood lymphocytes (CBL), and possibly < 31% of the T [thymus derived] cell-depleted lymphocyte population, carry receptors for P3HR-1 strain of EBV. The number of cells carrying receptors for EBV did not vary considerably among different blood lymphocyte populations from several normal donors. EBV adsorption on lymphocyte subpopulations showed that purified T cells and thymocytes did not adsorb EBV, in contrast to T cell-depleted lymphocyte populations and lymphoid cells from fetal liver and spleen. In CBL infected with EBV strain B95-8, EBNA was detected by anti-complement immunofluorescence as early as 18 h after infection. This indicates that EBNA is the earliest detectable EBV-determined intracellular antigen to appear after infection and before or during lymphocyte transformation by EBV. Transformation was observed only in lymphocyte cultures containing detectable thymus-independent B [bone marrow derived] cells but not in cultures of purified T cells. With 1 excetion (ES-B-1), all the EBV-transformed LCL from different origins carried surface-bound immunoglobulins (a B cell marker). These included also the 10 LCL obtained by infecting cultures of adherent cells from different donors. With regard to its surface markers, ES-B-1 appeared to be an exceptional EBV genome-carrying line, and it also lacked the ability to form spontaneous rosettes with sheep erythrocytes (a T cell marker). It is possible that ES-B-1 was derived from an atypical B cell or B cell precursor or from a so-called null cell transformed by EBV.