title: A critical review of the nature of the spongiform encephalopathy agent: protein theory versus virus theory.
abstract: All spongiform encephalopathies (SEs) result in brain disorders brought about by a slow virus. Since the origin of bovine SE (BSE), the infectious nature of the disease has been firmly established. Tubulofilamentous particles/scrapie termed nemavirus (NVP) and scrapie-associated fibrils (SAF) are ultrastructural markers, whereas protease-resistant protein (PrP(sc)) is a protein marker. The PrP molecules aggregate to form SAF. Each NVP consists of three layers: an outer protein coat, an intermediate ssDNA layer, and inner PrP/SAF. Therefore, ssDNA and PrP/SAF are physically associated with each other. The existence of at least 20 stable strains of SEs implies that a nucleic acid molecule serves as the information molecule. Animals inoculated with PrP(sc) do not develop the clinical disease, however, ssDNA purified from scrapie-hamster brains by alkaline gel electrophoresis mixed with binding proteins before inoculation developed the clinical disease. It appears that an "accessory protein" coded by the ssDNA of the NVP interacts with normal PrP(c) molecules, resulting in their conversion to PrP(sc)/SAF. The pathogenesis process in the infected animal, with increasing incubation periods, reveals that larger amounts of normal PrP molecules are modified to form SAF. This interferes with the normal supply of PrP to cell membranes, which become disrupted and eventually fragment, resulting in the vacuoles typical of those found in the SEs. Critical review of scientific literature has demonstrated that the agent contains a DNA genome.
authors.affiliation: Ken Bell International, Newcastle Upon Tyne NE2 3DH, United Kingdom. Harash@compuserve.com
authors.forename: Harash
authors.initials: H
authors.lastname: Narang
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D006224:Cricetinae; D004277:DNA, Single-Stranded / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D016643:Encephalopathy, Bovine Spongiform / Q000209:etiology* / Q000378:metabolism / Q000821:virology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018620:PrPSc Proteins / Q000378:metabolism / Q000472:pathogenicity; D011499:Protein Processing, Post-Translational
chemical_list: D004277:DNA, Single-Stranded; D004279:DNA, Viral; D009419:Nerve Tissue Proteins; D018620:PrPSc Proteins