SUSCEPTIBILITY TO A NEUROTROPIC VIRUS AND ITS CHANGING DISTRIBUTION IN THE DEVELOPING BRAIN IS A FUNCTION OF CNS MATURITY

Many major physiological changes occur within the rodent central nervo us system (CNS) during the first few postnatal weeks. These include ax onogenesis, synaptogenesis and myelination. Concomitant with CNS devel opment over this period, there is a decrease in susceptibility to many neurotropic virus infections in that infection of suckling animals re sults in lethal encephalitis whereas infection of weanling animals is not lethal. The events underlying this dramatic change in susceptibili ty have been unclear. Here we demonstrate that age-related virulence o f the neurotropic alphavirus, Semliki Forest virus is dependent upon a bility of the infection to spread in the CNS. This is not determined b y maturity of interferon, or specific immune responses or the blood br ain barrier, but by maturity of neuronal systems. Detailed study of th e course of infection in the cortex, hippocampus and cerebellum during their postnatal development indicates that as these and other neurona l systems mature they become resistant to spread of the virus and the pattern of infection changes from widespread to focal.