Re‐exposure of human lymphoblastoid cell lines to Epstein‐Barr virus

Abstract Human lymphoblastoid lines of various origins which harbour Epstein‐Barr 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 EBV‐specific early antigens (EA), 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 DNA‐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 EA 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 EBV‐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: (1) the response of human lymphoblastoid cells after re‐infection with EBV 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 EBV are refractory to re‐infection. It is suggested that the spontaneous synthesis of infectious virus favours the selection of resistant cells.