Prions, the name coined by Stanley Prusiner for protein-aceous infectious particles, have changed our understanding of infectious agents. All previously recognized pathogenic agents use nucleic acid, either DNA or RNA, to reproduce. Prions are abnormal structural variants of normal cellular proteins found in the membranes of neurons and other tissues (2,3).
Although scientific opinion generally supports Prusi-ner's 1982 hypothesis that TSEs are caused by abnormal prion proteins, other research groups continue looking for an unrecognized organism with nucleic acid (3), and one group continues to promote Spiroplasma sp. as a potential causative agent (20).
Prions are single molecules of about 250 amino acids and contain no nucleic acid. Abnormal prion protein is formed within the host by genetic mutation (eg, familial CJD), or by unknown means (eg, sporadic CJD), or enters the body via oral or other routes (eg, BSE, kuru, scrapie, etc), and proceeds to convert by contact normal protein into structurally aberrant forms. The conversion of normal cellular prion protein to the distorted prion conformation is characterized by a structural change from predominantly alpha helices to beta sheets (alpha helix:beta sheet 42:3 in normal prion protein, 30:43 in abnormal) (3,21). The distorted form has increased resistance to natural proteases and, as a result, accumulates in tissues, contributing to neuronal death and spongiform changes in the brain. Amyloid plaques are formed from remnants of prion protein in some, but not all, forms of TSE disease.
TSEs such as scrapie have been shown to exist as different "strains," evidenced by different incubation periods, lesion patterns, and chemical characteristics. Historically, strain differences in pathogenic organisms have always been associated with genetic differences represented by varying nucleic acid sequences (3). Strain differences in prion diseases appear to be from conformational differences of the same protein molecule. Functional behavior of the molecule is linked to the conformation and may influ ence susceptibility/resistance, infectious dose, virulence, disease pattern, and incubation period (13,14,17).
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