Photodegradation illuminates the role of polyanions in prion infectivity

Understanding the mechanism by which prion infectivity is encoded by the misfolded protein PrPSc remains a high priority within the prion field. Work from several groups has indicated cellular cofactors may be necessary to form infectious prions in vitro. The identity of endogenous prion conversion cofactors is currently unknown, but may include polyanions and/or lipid molecules. In a recent study, we manufactured infectious hamster prions containing purified PrPSc, co-purified lipid, and a synthetic photocleavable polyanion. The polyanion was incorporated into infectious PrPSc complexes, and then specifically degraded by exposure to ultraviolet light. Light-induced in situ degradation of the incorporated polyanion had no effect on the specific infectivity of the samples as determined by end-point dilution sPMCA and scrapie incubation time assays. Furthermore, prion strain properties were not changed by polyanion degradation, suggesting that intact polyanions are not required to maintain the infectious pr...