Virological and immunological studies in experimental SSPE

Subacute sclerosing panencephalitis (SSPE) is a progressive, fatal inclusion cell encephalitis of children and adolescents caused by persistent measles virus within the central nervous system (CNS). Because studies in man have failed to elucidate the pathogenesis of this condition, animal studies are necessary. Persistent infection of the hamster CNS can be achieved with a hamster adapted SSPE agent. Animals inoculated intracerebrally with this virus raise antibodies to all known antigens of measles virus and some display clinical signs and pathological changes similar to those noted in human SSPE. Persistent CNS infection occurs only if the hamster is inoculated at a critical age (18 to 25 days of life) or if adults are given transient immunosuppression during acute infection. The biological behavior of the virus isolated from hamster CNS appears to change from a complete to a defective state coincidents with the appearance of serum antibodies to measles virus. Adult hamsters from whom the thymus was removed in the newborn period develop a subacute, uniformly fatal infection when exposed to the SSPE agent. These studies suggest that SSPE may develop in man when measles virus invades the immature CNS at a critical age or when the immune system is uncompletely developed or is inhibited. The finding that transient immunosuppression allows development of persistent CNS infection in adults suggest that immunological malfunction is the significant factor. Of interest, antibody appears to alter viral behavior to a defective, intracellular state thus enhancing viral survival in the host. Once a defective, CNS infection is achieved, lack of, or inhibition of the host cellular immunes response allows it to persist. Methods of therapy in light of these findings will be discussed.