Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome

Most of the small number of cases of poliomyelitis which occur in countries where Sabin's attenuated poliovirus vaccines are used are temporally associated with administration of vaccine and involve polioviruses of types 2 and 3 (ref. 1). Recent studies have provided convincing evidence that the Sabin type 2 and 3 viruses themselves may revert to a neurovirulent phenotype on passage in man2–6. We report here that a point mutation in the 5′ noncoding region of the genome of the poliovirus type 3 vaccine consistently reverts to wild type in strains isolated from cases of vaccine-associated poliomyelitis. Virus with this change is rapidly selected on passage through the human gastrointestinal tract. The change is associated with a demonstrable increase in the neurovirulence of the virus.