This study showed that in sheep persistently infected with Visna virus, the agent underwent
progressive antigenic drift over a period of years in concert with development of
neutralizing antibody to pre-existing strains of virus. This constant evolution of stable
antigenic mutants appears to be a special adaptation of this virus to its host. Similar antigenic
alterations have been observed in the aetiological agents causing recurrent acute
diseases of man and animals such as trypanosomiasis (Vickerman, I974), malaria (Brown,
I974) and equine infectious anaemia (Kono et al. I973). The slow process of mutation and
selection observed in vivo can be greatly accelerated in cell cultures since we have recently
shown that cell cultures inoculated with a plaque suspension of I514 virus and maintained
in medium containing anti-I5~4 antibody produced a stable mutant within 3 weeks
(Narayan et al. ~977a; O. Narayan, unpublished data). The only limitation for progressive
mutation in the cell culture system appeared to be the lack of appropriate antibody to the
newly evolved mutants for further selection of new mutants. This obstacle was overcome in
the animal in which virus can replicate, albeit very slowly, and in which antibody can be
stimulated, thus providing the environment for repetitive cycles of virus growth, antibody
induction, mutation and selective growth of mutants.