The molecular basis of poliovirus neurovirulence

Species specificity of poliovirus (PV) is mostly governed by host cellular molecules that serve as the PV receptor (PVR). Molecular cloning of the gene and cDNAs of human PVR and the subsequent development of PV-sensitive transgenic (Tg) mice carrying the human PVR gene made it possible to investigate molecular mechanisms for PV-specific dissemination in the whole body. After intravenous inoculation which makes artificial viremia, poliovirus appears to enter the central nervous system (CNS) at a fairly high rate via the blood brain barrier, suggesting existence of a specific permeation system for PV. This main dissemination process does not require PVR. After intramuscular inoculation, PV appears to be incorporated by endocytosis at synapses, and the endosomes containing PV transported through axons to neuron cell body, where viral replication occurs. Efficiency of viral multiplication in the CNS probably determines the neurovirulence level, which differs between PV strains. An important determinant for neurovirulence phenotype resides in the internal ribosomal entry site (IRES). This has led us to a concept of "IRES-dependent virus tropism".