Re-exposure of human lymphoblastoid cell lines to Epstein-Barr virus.

Human lymphoblastoid lines of various origins which harbour Epstein-Burr virus (EBV)-specific nucleic acid were re-exposed to EBV. Following infection, cells of the non-virus-producing lines, Raji and S 95, predominantly synthesized EB V-specific early antigens ( E A ) , whereas only a small percentage of cells revealed viral capsid antigens ( VCA). In Raji cells, the number of VCA-producing cells was paralleled by the percentage of virus-specific D NA-synthesizing cells. In S 95 cells, however, viral DNA-synthesizing cells exceeded the number of VCA-producing cells by a factor of more than 10. Induction of E A in Raji cells was dose-dependent and inversely related to cell growth. Irradiation of the virus by ultraviolet light prior to infection led to reduced infectivity. This reduction seemed to follow single-hit kinetics. Raji cells, previously re-exposed to EBV, showed reduced EA induction after re-infection with EBV, as compared to Raji control cells not previously exposed. Of 10 lines which spontaneously synthesize EB V-specific antigens, seven lines proved to be refractory to re-infection, whereas three were as susceptible as the Raji and S 95 controls. From three of the refractory lines infectious virus could be recovered from the culture medium prior to infection. These results permit the following interpretations: ( I ) the response of human lymphoblastoid cells after re-infection with EB V results from the infecting virus and not from stimulation of endogenous genomes; ( 2 ) cells demonstrating EA synthesis ultimately die; (3 ) re-exposure to EBV increases the resistance to re-infection of the surviving cells; and ( 4 ) cell lines producing infectious EBVare refractory to re-infection. It is suggested that the spontaneous synthesis of infectious virus favours the selection of resistant cells.