RAPID ATTENUATION OF VEE VIRUS IN CHRONICALLY INFECTED SUSPENDED L CELLS

L cells grown in serum-free defined medium readily became chronically infected with Venezuelan equine encephalomyelitis VEE virus whereas cells grown in serum-free lactalbumin medium did not. The addition of serum eliminated the ability of the defined medium to induce the chronic state of infection. During the first 48 hours after inoculating L cell cultures, the cells underwent an acute phase of viral activity that resulted in widespread cell destruction and 10 to the 8th power to 10 to the 9th power MICLD50 of virus per ml. The acute phase was followed by an apparent transitional phase with yields of approximately 10,000 MICLD50 of virus per ml, then a resumption of cell multiplication. As the cultures progressed into the chronically infected phase, virus yields fluctuated between 1000 and 10 to the 5.5 power MICLD50 per ml. Finally, the virus lost its ability to produce a lethal intraperitoneal infection at 8 days for rabbits, at 29 days for mice, at 72 days for guinea pigs, and at 112 days for hamsters. The qualitative changes in the viral populations that were derived from the culture occurred, therefore, independently of concomitant quantitative changes. During the course of chronic infection, the cells were resistant to a challenge with homotypic virus.