Succession of Mutations in the Sabin Strain of Type 3 Poliovirus Replicating in the Central Nervous System of Monkeys

Abstract

Sabin strains of oral poliovirus vaccine (OPV) undergo limited genetic changes during replication in cell cultures, the gastrointestinal tract of vaccinees, and the central nervous system of monkeys. Some of these changes are associated with loss of attenuation markers. Here we report the dynamics of mutant accumulation in the Sabin strain of poliovirus type 3 inoculated intraspinally into monkeys. Thr → Ile reversion in amino acid 6 of VP1 (2493 C → U) occurred within the first few days postinoculation (p.i.), but decreased on later days and completely disappeared by Day 17 p.i. 472 U → C reversion in the 5′-untranslated region appeared to accumulate slower and by Day 17 completely substituted for the vaccine-type nucleotide at this site. These results indicate that experimental infection of the central nervous system of monkeys consists of early and late phases in which a different genetic constitution of the virus is favored. In several isolates one additional neurovirulent revertant was found: a Phe → Ser at amino acid 91 of VP3 (2034 U → C). Since this mutation was never detected in vaccine lots and is strongly selected against in cell cultures at temperatures below 38.5°, it does not threaten the safety of OPV.