[Effect of the method of passage on the biological properties of attenuated alphavirus strains]

Experiments with attenuated clones of Venezuelan equine encephalomyelitis virus and Eastern equine encephalomyelitis virus were carried out to study the regularities in changes of biological properties of virus in "undiluted" passages and in passages by subcultivation of small doses. In the latter case the biological activity of the virus remained at the initial low level but in "undiluted" passages it increased, due to accumulation in the population of clones with altered plaque phenotype and increased reproductive potential. In a number of cases this virus had a higher level of residual virulence than the original one. The evidence that the main source of virus variability in the "undiluted" passages lies, in genetic interaction in which defective virus takes part, is presented. Mixed infection with participation of defective interfering particles and the genetic interaction occurring in it are considered to be the mechanism which is conducive to restoration of biological activity of alphaviruses.