Manuelidis Laboratory

Clinical and experimental models of dementia with an emphasis on Transmissible Encephalopathies especially human CJD. Many people believe the infectious agent is a misfolded form of host “prion protein” (PrP). However, this misfolded PrP amyloid appears to be the result of infection by an environmental pathogen that uses the cell’s PrP for entry and/or replication. Subcellular fractionations here have shown the agent is of viral size (20-25nm in diameter) and, as other viruses, can be rapidly inactivated by 3M GdnHCl), a treatment that does not destroy PrP amyloid. “Infectious PrP” is also claimed to lack nucleic acid. Nevertheless, all purified highly infectious particle fractions contain long nucleic acids (3,000-16,000 nucleotides), and 3 logs (>99.8%) of their infectivity is abolished selective nuclease digestion. A TSE agent specific nucleic acid could be the basis for different TSE agent strains. TSE agents are a paradigm for the plethora of new uncharacterized environmental viruses that are likely to have a major role in latent and late-onset diseases.