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Journal of Virology, July 2002, p. 6791-6799, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6791-6799.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Long-Term Circulation of Vaccine-Derived Poliovirus That Causes Paralytic Disease

Elena A. Cherkasova,1,2 Ekaterina A. Korotkova,1 Maria L. Yakovenko,1 Olga E. Ivanova,3 Tatyana P. Eremeeva,3 Konstantin M. Chumakov,2 and Vadim I. Agol1,3*

A. N. Belozersky Institute of Physical-Chemical Biology, Moscow State University, Moscow 119899,1 M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782, Russia,3 Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 208522

Received 28 December 2001/ Accepted 3 April 2002

Successful implementation of the global poliomyelitis eradication program raises the problem of vaccination against poliomyelitis in the posteradication era. One of the options under consideration envisions completely stopping worldwide the use of the Sabin vaccine. This strategy is based on the assumption that the natural circulation of attenuated strains and their derivatives is strictly limited. Here, we report the characterization of a highly evolved derivative of the Sabin vaccine strain isolated in a case of paralytic poliomyelitis from a 7-month-old immunocompetent baby in an apparently adequately immunized population. Analysis of the genome of this isolate showed that it is a double (type 1-type 2-type 1) vaccine-derived recombinant. The number of mutations accumulated in both the type 1-derived and type 2-derived portions of the recombinant genome suggests that both had diverged from their vaccine predecessors ~2 years before the onset of the illness. This fact, along with other recent observations, points to the possibility of long-term circulation of Sabin vaccine strain derivatives associated with an increase in their neurovirulence. Comparison of genomic sequences of this and other evolved vaccine-derived isolates reveals some general features of natural poliovirus evolution. They include a very high preponderance and nonrandom distribution of synonymous substitutions, conservation of secondary structures of important cis-acting elements of the genome, and an apparently adaptive character of most of the amino acid mutations, with only a few of them occurring in the antigenic determinants. Another interesting feature is a frequent occurrence of tripartite intertypic recombinants with either type 1 or type 3 homotypic genomic ends.

* Corresponding author. Mailing address: Institute of Poliomyelitis, Moscow Region 142782, Russia. Phone: 7 (095) 439 9026. Fax: 7 (095) 439 9321. E-mail: agol{at}belozersky.msu.ru.

Journal of Virology, July 2002, p. 6791-6799, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6791-6799.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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