A HOST-DEFENSE ROLE FOR A NATURAL ANTIVIRAL SUBSTANCE IN THE NERVOUS-SYSTEM

The pathogenesis of virus infections of the nervous system (NS) is reg ulated by host defenses. The defensive role of a major constitutive an tiviral substance was studied by determining its distribution in the h uman nervous system, its concentration and the ability of this viral i nhibitor to protect mice against viral infection. The 4000 kDa inhibit or complex in the human nervous system was detected in brain gray and white matter, spinal cord, and sciatic nerve but not in human cerebros pinal fluid. The inhibitor was found in the extracellular medium incub ated with minced murine brain. The inhibitory titer ranged from approx imately 50 to 200 antiviral units per gram against polio 1, Semliki Fo rest, Banzi, mengo, Newcastle disease and herpes simplex 1 viruses. Th e inhibitor is composed of lipid and essential protein and carbohydrat e moieties as determined by enzymatic inactivation. Protection of inhi bitor-treated mice was demonstrated against both an alphavirus and a p icornavirus. Thus a natural defensive role for the broadly antiviral i nhibitor is suggested by its constitutively high concentration, wide d istribution in nervous system tissues, presence in extracellular fluid and its ability to provide protection in infected mice. (C) 1998 Else vier Science B.V. All rights reserved.