Spontaneous cessation of Friend murine leukemia virus production by leukemia cell line Y57: overgrowth by nonproducer cells.

Cell line Y57, obtained from a (C57BL/10 X A.BY)F1 mouse made leukemic with Friend virus complex (FV), spontaneously ceased FV production in vitro after 20 passages. By limiting dilution cloning, the incidence of non-virus-producing cells was found to increase with sequential passage. Nonproducer cells apparently arose spontaneously and were able to increase in number relative to producer cells because the growth rate of nonproducer cells was more rapid than the rate at which virus could reinfect them. Nonproducer clones all contained the defective spleen focus-forming virus in a latent but rescuable form but showed defects in helper virus env and gag gene product synthesis. Stable long-term virus-producing clones were obtained both by cloning at early in vitro passages or by cloning immediately after reinfection of nonproducer cells with FV.