HUMAN AND EXPERIMENTAL SPONGIFORM ENCEPHALOPATHIES - RECENT PROGRESS IN PATHOGENESIS

The spongiform encephalopathies belong to the group of "slow virus infections" of the nervous system, characterized by a long incubation period, a protracted course and involvement of the nervous system with a lethal outcome. In contrast to the conventional virus infections, such as visna in sheep and progressive multifocal leukoencephalopathy (PML) in humans, the etiological agent for the spongiform encephalopathies has not been clearly defined. The known forms in animals are scrapie in sheep and goats, transmissible mink encephalopathy, and chronic wasting disease of mule deer and elk. In humans, the three known forms are Kuru, now mainly of historical interest, Creutzfeldt-Jakob (CJ) disease and the syndrome of Gerstmann-Straussler-Scheinker (GSS). An important feature of these diseases is the lack of an immune response by the host, which is reflected in the absence of inflammatory infiltrates in the affected tissues. In this editorial the two most important hypotheses on the etiology and pathogenesis of this group of conditions will be discussed. The "prion" hypothesis considers the possibility that a protein, derived from a normal component of the neuronal membranes may have a leading role, not only in the infectivity and transmissibility of these diseases, but in the pathological changes that ensue. A single host gene would code for both the normal and altered proteins. The altered protein would be partially insoluble and would result in the deposition of fibrils and rods which would precipitate in the form of amyloid. Since the involved protein would be coded for by the host, there would be no immune response against it. The viral hypothesis, on the other hand, maintains that the difficulties in isolating a nucleic acid in the infective agent are probably due to technical limitations more than to its real absence. A scrapie-specific nucleic acid, for instance, could be enveloped in a protein encoded by the host, so that the immune system would not be stimulated. Alternatively, a conventional virus, particularly a retrovirus, might be responsible for these diseases, since retroviruses can be integrated into the host genome, thus remaining hidden from the immune system of the host. Data, both in favor and against these two major hypotheses will be briefly presented.