The complete nucleotide sequence ofthe genome of the type 1 poliovirus vaccine strain (LSc,2ab) was determined by using molecular cloning and rapid sequence analysis techniques. The restriction fragments of double-stranded cDNA synthesized from the vaccine strain RNA were inserted into the adequate sites of cloning vector pBR322. Sequence analysis of the cloned DNAs revealed that the virion RNA molecule was 7,441 nucleotides long and polyadenylylated at the 3' terminus. When the nucleotide sequence was compared with that of the genome of the virulent parental strain (Mahoney), 57 base substitutions were observed to be scattered all over the genome. Of these, 21 resulted in amino acid changes in a number of viral proteins. A cluster of amino acid changes is located in the viral coat proteins, especially in the NH2-terminal halfofthe viral capsid protein VP1.These results may imply that the mutations in the VP1 coding region contribute to attenuation.The genome ofpoliovirus is a single-stranded RNA with positive polarity, in which all of the viral genetic information is stored (1). This genomic RNA is composed of =7,500 nucleotides, polyadenylylated at the 3' terminus (2) and covalently attached to a genome-linked protein (VPg) at the 5' terminus (3-6). Re PVl(Sab)] is a live vaccine strain derived from the PV1(M) by spontaneous mutations during the attenuation process (9, 10).To determine the molecular basis for the biological differences between virulent and attenuated poliovirus strains, the sequences of large and unique RNase Ti-and A-resistant ohigonucleotides of PV1(M) and PV1(Sab) have been compared. We have shown that mutations detected by oligonucleotide analysis were caused by single base substitutions and appeared to be scattered all over the genome (11).For further comparative sequence studies, the restriction fragments obtained from double-stranded cDNA of the PV1(Sab) genome have been cloned (12). We report here the complete 7,441-nucleotide sequence of the PV1(Sab) genome, and the mutation sites were identified by comparison of our sequence with the known sequence of the PV1(M) genome (7,8).

No abstract

No abstract

No abstract