ENDOSYMBIOTIC RELATIONSHIP BETWEEN ANIMAL VIRUSES AND HOST CELLS. A STUDY OF RABIES VIRUS IN TISSUE CULTURE.

RE cultures infected with a fixed rabies virus were studied. The virus can propagate itself in these cells for an indefinite period of time without interfering with cell growth. The present study characterizes this truly endosymbiotic relationship. Virus-specific antigen was detected in the cytoplasm of each cell by fluorescein-labeled antirabies serum but only 4 to 5 per cent of the cells released infectious virus. All cells undergoing division showed viral antigen throughout the mitotic process. Also, the growth rate, plating efficiency, and morphological characteristics of both the infected and control cultures were identical. No difference was detected between the RE and the RE-CVS cell populations by RNA and DNA labeling experiments, using H(3)-thymidine, and H(3)-uridine. Although antirabies serum effectively inhibited the spread of extracellular virus, it did not interfere with cell-to-cell transmission of the virus during mitosis, in the course of 9 cell transfers during 53 days. RE-CVS cells, when exposed to fresh antirabies serum, lysed completely but inactivated serum had no lytic effect. The addition of fresh hamster complement to the inactivated serum restored its cytolytic properties. The serially passaged RE-CVS virus gradually became less virulent for mice and displayed a weak antigenicity in the mouse protection test. Another feature of the RE-CVS cell system is its resistance to infection with homologous and heterologous viruses despite the apparent absence of an interferon-like substance.