A comparison of brain lysosomal enzyme activities in four experimental togavirus encephalitides

Abstract

Experimental encephalitis was produced in mice by inoculations of Langat, Chikungunya or Sindbis viruses or of an avirulent strain of Semliki forest virus. These infections resulted in disease processes which ranged from clinically inapparent to fatal. In all cases a rise in activity of β-glucuronidase was observed which correlated with the appearance of monocytic perivascular infiltration, microgliosis and to a lesser extent astrocytic hypertrophy. Mice infected lethally with Langat or Chikungunya virus developed severe necrosis of the cerebrum accompanied by a decrease in the activity of N- acetyl-β- d- glucosaminidase , acid phosphatase and aryl sulphatase. Increases in the activity of N- acetyl-β- d- glucosaminidase and acid proteinase were observed during the encephalitides from which mice were to recover, but both acid phosphatase and aryl sulphatase remained at control levels. The increases in enzyme activity in each avirulent infection occurred at the same time that brain virus titres began to fall rapidly and serum antibody levels were detectable by neutralisation tests. The highest levels of acid proteinase activity were obtained in Semliki forest virus infection in which foci of cerebellar demyelination were also seen. Lysosomal enzyme production may be important as a cause of demyelination and comparisons have been made in this context with findings in multiple sclerosis. It is suggested that avirulent Semliki forest virus infection of mice may represent a useful model for the study of human demyelinating diseases which may be associated with virus infections of the CNS.