ABSTRACT On the eve of global eradication of a second human disease, paralytic poliomyelitis, we propose to review current understanding of the molecular mechanisms of attenuation of the causal agent, poliovirus. Particular emphasis will be given to the role of the 5’ non-coding region of the viral RNA genome in pathogenesis. This topic has incited much interest over the last twenty years, since the discovery that all three attenuated vaccine strains developed by Albert Sabin harbor a single point mutation at essentially the same site within the 5’ non-coding region, and that these mutations have reverted in neurovirulent viruses excreted by vaccinees. Despite extensive endeavours from several research groups, the mechanism of attenuation involving these mutations has remained largely obscure. Recent molecular genetic studies from our own and other laboratories have shed interesting insights into the phenomenon, and have allowed to precise in detail the mechanisms of poliovirus attenuation. These mechanisms are of particular relevance to the potential control of other closely related neurotropic viruses, which cause diseases such as infantile meningitis and encephalitis.
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