RANDOM SELECTION - A MODEL FOR POLIOVIRUS INFECTION OF THE CENTRAL-NERVOUS-SYSTEM

Mixed infections occur in the natural environment, and also result fro m the use of mixed live vaccines. Some recipients of the trivalent ora l poliovirus vaccine develop vaccine-associated paralytic poliomyeliti s (VAPP). Numerous serotypes and recombinant genotypes of vaccine-deri ved polioviruses may be found in stool samples from such cases. To inv estigate the relationship between the multiplication of various genoty pes at the primary replication site in the gut and the infection outco me in the central nervous system (CNS), the viruses excreted on consec utive days by two patients with VAPP were compared with the viruses is olated from the CNS. The genotypes from stools were numerous and varie d with time in both cases, suggesting a multiplication of the viruses in multiple foci in the gut, Where the CNS isolated virus clearly corr esponded to one of the many viruses detected in stool, this virus was unexpectedly less neurovirulent than others isolated from stool, To as sess the mechanism by which viruses with different degrees of neurovir ulence are selected in the CNS, transgenic mice sensitive to polioviru s infection were inoculated extraneurally with mixtures of two phenoty pically different viruses at different neuropathogenic doses. The viru s(es) inducing neurological disease was then isolated from the CNS. At less than 100% input neuropathogenic dose of both inoculated viruses, individual mice were affected stochastically by the virus variants fr om the mixture, Extrapolated to humans, this selection pattern might e xplain the occurrence of CNS infections with less neurotropic viruses derived from an extraneural pool containing also highly neurotropic vi ruses.