HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Narang, H. Search for Related Content PubMed PubMed Citation Articles by Narang, H.

---

MINIREVIEW

A Critical Review of the Nature of the Spongiform Encephalopathy Agent: Protein Theory Versus Virus Theory¹

Ken Bell International, Newcastle Upon Tyne NE2 3DH, United Kingdom

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.

Key Words: Creutzfeldt-Jakob disease • bovine spongiform encephalopathy • Kuru • nemavirus • protease-resistant protein (PrP) • scrapie • scrapie-associated fibrils

This article has been cited by other articles:

				J. G. Safar, K. Kellings, A. Serban, D. Groth, J. E. Cleaver, S. B. Prusiner, and D. Riesner Search for a Prion-Specific Nucleic Acid J. Virol., August 15, 2005; 79(16): 10796 - 10806. [Abstract] [Full Text] [PDF]

				C. Castro-Fernandez, G. Maya-Nunez, and P. M. Conn Beyond the Signal Sequence: Protein Routing in Health and Disease Endocr. Rev., June 1, 2005; 26(4): 479 - 503. [Abstract] [Full Text] [PDF]