Differences between laboratory strains of Epstein-Barr virus based on immortalization, abortive infection and interference

Abstract

Biological activities of extracellular Epstein-Barr virus (EBV) from two laboratory strains, namely P3J-HR-1 (P-H) from Burkitt's lymphoma and B95-8 (B95) from infectious mononucleosis, were compared. Virus stocks from both sources contained approximately the same number of virions. Virus from the P-H line induced early antigen in six non-producer EBV-genome carrier cell lines; virus from B95 did not induce early antigen. Extracellular virus from B95 regularly caused lymphocytes from human umbilical cords to form continuous lines (immortalization); P-H virus did not cause primary cultures of human lymphocytes to grow continuously. B95 virus stimulated DNA synthesis, as determined by the rate of incorporation of 3H-thymidine into acid-insoluble material; P-H virus did not stimulate DNA synthesis. Pretreatment of lymphocytes with undiluted P-H virus inhibited immortalization and stimulation of DNA synthesis by B95 virus. The inhibitory properties of the P-H virus were sedimented at 100 000 g and inactivated by heat and UV irradiation; interference by the P-H virus was neutralized by human serum with antibody to EBV and not by antibody-negative human serum. The hypothesis most consistent with these results is that the P-H virus is defective in gene(s) needed for initiation of immortalization. We speculate that the absence of this gene allows early antigen to be expressed upon superinfection of non-producer cell lines. The availability of two laboratory strains of two laboratory strains of EBV that differ in biological behaviour provides starting material for analysis of the mechanism of lymphocyte immortalization by EBV and of virus structural differences that affect immortalization.