Morales Rodrigo, Abid Karim, Soto Claudio
Protein Misfolding Disorders Laboratory, George and Cynthia Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555-0646, USA.
Biochim Biophys Acta. 2007 Jun;1772(6):681-91. doi: 10.1016/j.bbadis.2006.12.006. Epub 2006 Dec 15.
Prions are unconventional infectious agents responsible for transmissible spongiform encephalopathies. Compelling evidences indicate that prions are composed exclusively by a misfolded form of the prion protein (PrP(Sc)) that replicates in the absence of nucleic acids. One of the most challenging problems for the prion hypothesis is the existence of different strains of the infectious agent. Prion strains have been characterized in most of the species. Biochemical characteristics of PrP(Sc) used to identify each strain include glycosylation profile, electrophoretic mobility, protease resistance, and sedimentation. In vivo, prion strains can be differentiated by the clinical signs, incubation period after inoculation and the lesion profiles in the brain of affected animals. Sources of prion strain diversity are the inherent conformational flexibility of the prion protein, the presence of PrP polymorphisms and inter-species transmissibility. The existence of the strain phenomenon is not only a scientific challenge, but it also represents a serious risk for public health. The dynamic nature and inter-relations between strains and the potential for the generation of a large number of new prion strains is the perfect recipe for the emergence of extremely dangerous new infectious agents.
朊病毒是导致传染性海绵状脑病的非常规感染因子。有力证据表明，朊病毒仅由朊病毒蛋白的错误折叠形式（PrP(Sc)）组成，其在没有核酸的情况下进行复制。朊病毒假说面临的最具挑战性的问题之一是感染因子存在不同毒株。在大多数物种中都已对朊病毒毒株进行了特征描述。用于鉴定每个毒株的PrP(Sc)的生化特性包括糖基化谱、电泳迁移率、蛋白酶抗性和沉降特性。在体内，朊病毒毒株可通过临床症状、接种后的潜伏期以及受感染动物大脑中的病变特征来区分。朊病毒毒株多样性的来源包括朊病毒蛋白固有的构象灵活性、PrP多态性的存在以及种间传播性。毒株现象的存在不仅是一项科学挑战，也对公共卫生构成严重风险。毒株之间的动态性质和相互关系以及产生大量新朊病毒毒株的可能性，是极其危险的新感染因子出现的完美条件。
