The Molecular and Functional Basis of Poliovirus Attenuation and Host Range

Abstract

Poliovirus is the causative agent of poliomyelitis, an acute disease of the central nervous system (CNS). For 50 years after its isolation in 1909, research on the virus was aimed at providing the necessary information on antigenic types, pathogenesis, and immunity so that vaccines could be developed. After two effective vaccines were produced, research on poliovirus turned toward understanding events that occur in infected cells, such as viral RNA and protein synthesis and inhibition of host macromolecular synthesis. Three developments of the early 1980s once again altered the direction of poliovirus research: the determination of the nucleotide sequence of the poliovirus genome and mapping of the viral polypeptides [1], the demonstration that cloned poliovirus cDNA is infectious in cultured cells [2], and the resolution of the three-dimensional structure of the poliovirion [3]. Although these findings have clearly facilitated the study of poliovirus replication, they have also made it possible to address previously unanswered questions about poliovirus neurovirulence. This chapter will summarize and evaluate recent progress made in understanding the molecular and functional basis for the attenuation of the poliovirus vaccine strains and for the restricted host range of the virus.