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Comparison of poliovirus recombinants: accumulation of point mutations provides further advantage

¹ National Institute for Health and Welfare;
² Research Institute of Epidemiology and Microbiology, Minsk, Belarus

³ E-mail: carita.savolainen-kopra{at}thl.fi

The roles of recombination and accumulation of point mutations in the origin of new characteristics of polioviruses have been hypothesized, but what is essential to evolution is not clearly known. We studied phenotypic differences between recombinant strains of polioviruses isolated from successive stool specimens of an OPV recipient. The studied strains included three PV2/PV1 recombinants with increasing mutations in the VP1 gene, two of the three with an amino acid change IT in the DE-loop of VP1, their putative PV1 parent and Sabins 1 and 2. Growth curves were determined in three cell lines; CaCO, SK-N-SH and HeLa cells. The main observation was a higher growth rate, between 4-6 hours p.i., of the two recombinants with the IT substitution. All recombinants beat parental strains in the exponential phase of the replication cycle. In a temperature sensitivity test the IT substituted recombinants replicated equally well at an elevated temperature. Complete genome sequencing of the three recombinants revealed 12 (3), 19 (3) and 27 (3) nucleotide (amino acid) differences to Sabin, respectively. Mutations located in regions defining attenuation, temperature sensitivity, antigenicity and CRE. Recombination site was in the 5^'-end of 3D. In a competition assay the most mutated recombinant beat parental Sabin in all three cell lines, strongly suggesting advantage of this virus. Two independent intertypic recombinants, PV3/PV1 and PV3/PV2 also showed similar growth advantages, but they again contained several point mutations. Thus our data defend the hypothesis that accumulation of certain advantageous mutations plays a key role in gaining increased fitness.

Received 9 February 2009; accepted 28 April 2009.