Evolution of circulating wild poliovirus and of vaccine-derived poliovirusin an immunodeficient patient: a unifying model

We determined nucleotide sequences of the VP1 and 2AB genes and portions of the 2C and 3D genes of two evolving poliovirus lineages: circulating wild viruses of T geotype and Sabin vaccine-derived isolates from an immunodefic ient patient. Different regions of the viral RNA were found to evolve nonsy nchronously, and the rate of evolution of the 2AB region in the vaccine-der ived population was not constant throughout its history. Synonymous replace ments occurred not completely randomly, suggesting the need for conservatio n of certain rare codons (possibly to control translation elongation) and t he existence of unidentified constraints in the viral RNA structure. Nevert heless the major contribution to the evolution of the two lineages came fro m linear accumulation of synonymous substitutions. Therefore, in agreement with current theories of viral evolution, we suggest that the majority of t he mutations in both lineages were fixed as a result of successive sampling , from the heterogeneous populations, of random portions containing predomi nantly neutral and possibly adverse mutations. As a result of such a mode o f evolution, the virus fitness may be maintained at a more or less constant level or may decrease unless more-fit variants are stochastically generate d. The proposed unifying model of natural poliovirus evolution has importan t implications for the epidemiology of poliomyelitis.