Chronic Infectious Neuropathic Agents: Possible Mechanisms of Pathogenesis

Abstract

In discussing the pathogenesis of disease produced by chronic infectious neuropathic agents, three problems are immediately apparent: (1) explaining the long incubation period, (2) explaining the slow evolution of clinical disease and the unusual pathological findings often associated with these diseases, and (3) explaining the role of antibody in the prevention or causation of the disease. In the classic “slow virus infections” of sheep (Sigurdsson, 1954), visna and scrapie, the incubation period extends from months to years and is followed by a subacute neurological disease lasting for weeks to months. Visna, a demyelinating disease of the central nervous system (CNS), occurs long after the appearance of neutralizing antibody (Gudnadóttir and Pálsson, 1966); while scrapie, a non-inflammatory degenerative disease of the CNS, occurs with no evidence of antibody formation (Gajdusek etal., 1965). Very little experimental data exist to explain these curious phenomena in visna and scrapie, and discussion of their mechanisms of pathogenesis must rely largely on speculation and by analogy to other diseases. Several viruses, such as rabies, mumps, and lymphocytic choriomeningitis, provide more facile laboratory models and cause diseases in experimental animals which display one or more characteristics of slow virus infections of the CNS. Therefore, studies of these agents may provide some insights into mechanisms of disease production by slow viruses.

This work was supported by Research Grant NB-05244 from the National Institute of Neurological Diseases and Blindness, National Institute of Health Bethseda, Md.