Comparison of the complete nucleotide sequences of the genomes of the neurovirulent poliovirus P3/Leon/37 and its attenuated Sabin vaccine derivative P3/Leon 12a1b.

As part of a study into the molecular basis of attenuation and reversion to neurovirulence in the Sabin poliovirus vaccines, we have determined the complete nucleotide sequence of a cloned DNA copy of the genome of P3/Leon/37, the neurovirulent progenitor of the type 3 Sabin vaccine strain, P3/Leon 12a1b. Comparison of the sequence with that which we previously obtained for the vaccine strain Stanway, G., Cann, A. J., Hauptmann, R., Hughes, P., Clarke, L. D., Mountford, R. C., Minor, P. D., Schild, G. C. & Almond, J. W. (1983) Nucleic Acids Res. 11, 5629-5643 indicates that attenuation has been brought about by a maximum of 10 point mutations, at least 5 of which are likely to be of minor significance. Predicted amino acid sequences of all the known virus-encoded proteins show that amino acid substitutions have occurred at only three positions. Two of these are in structural proteins (i.e., Ser----Phe in VP3 and Lys----Arg in VP1), and the third, Thr----Ala, is in the nonstructural protein P2-3b. The distribution and nature of nucleotide and amino acid sequence differences suggest that a single base substitution may be responsible for the attenuated phenotype of the vaccine strain.