The protein-only hypothesis predicts that infectious mammalian prions are composed solely of PrP^Sc, a misfolded conformer of the normal prion protein, PrP^C. However, to date, all wild type protein-only PrP^Sc preparations lack significant levels of prion infectivity. Using a systemic biochemical approach, our laboratory isolated and identified two different endogenous cofactor molecules, RNA (Deleault et al., 2003 [50]; Deleault et al., 2007 [59]) and phosphatidylethanolamine (Deleault et al., 2012 [61]; Deleault et al., 2012 [18]), which facilitate the formation of prions with high levels of specific infectivity, leading us to propose to the alternative hypothesis that cofactor molecules are required to form wild type infectious prions (Deleault et al., 2007 [59]; Deleault et al., 2012 [18]; Geoghegan et al., 2007 [57]). In addition, we found that purified cofactor molecules restrict the strain properties of chemically defined infectious prions (Deleault et al., 2012 [18]), suggesting a “cofactor selection” model in which natural variation in the distribution of strain-specific cofactor molecules in different parts of the brain may be responsible for strain-dependent patterns of neurotropism (Deleault et al., 2012 [18]; Geoghegan et al., 2007 [57]).

唯一的蛋白假说预测，感染哺乳动物朊病毒完全的朊蛋白组成的^钪，正常的朊蛋白，朊病毒的错误折叠的构象^Ç。然而，迄今为止，所有野生型仅蛋白质 PrP ^Sc制剂缺乏显着水平的朊病毒感染性。使用系统生化方法，我们的实验室分离并鉴定了两种不同的内源性辅因子分子 RNA（Deleault 等人，2003 [50]；Deleault 等人，2007 [59]）和磷脂酰乙醇胺（Deleault 等人，2012 [61] ]; Deleault et al., 2012 [18])，这有助于形成具有高水平特异性感染性的朊病毒，导致我们提出替代假设，即形成野生型感染性朊病毒需要辅因子分子（Deleault 等人，2012 年）。 , 2007 [59]; Deleault et al., 2012 [18]; Geoghegan et al., 2007 [57])。此外，我们发现纯化的辅因子分子限制了化学定义的传染性朊病毒的菌株特性（Deleault et al., 2012 [18]），