A 25 nm virion is the likely cause of transmissible spongiform encephalopathies

AbstractThe transmissible spongiform encephalopathies (TSEs) such as endemic sheep scrapie, sporadic human Creutzfeldt‐Jakob disease (CJD), and epidemic bovine spongiform encephalopathy (BSE) may all be caused by a unique class of “slow” viruses. This concept remains the most parsimonious explanation of the evidence to date, and correctly predicted the spread of the BSE agent to vastly divergent species. With the popularization of the prion (infectious protein) hypothesis, substantial data pointing to a TSE virus have been largely ignored. Yet no form of prion protein (PrP) fulfills Koch's postulates for infection. Pathologic PrP is not proportional to, or necessary for infection, and recombinant and “amplified” prions have failed to produce significant infectivity. Moreover, the “wealth of data” claimed to support the existence of infectious PrP are increasingly contradicted by experimental observations, and cumbersome speculative notions, such as spontaneous PrP mutations and invisible strain‐specific forms of “infectious PrP” are proposed to explain the incompatible data. The ability of many “slow” viruses to survive harsh environmental conditions and enzymatic assaults, their s