A closer look at prion strains

Abstract

Prions are infectious proteins that are responsible for transmissible spongiform encephalopathies (TSEs) and consist primarily of scrapie prion protein (PrP^Sc), a pathogenic isoform of the host-encoded cellular prion protein (PrP^C). The absence of nucleic acids as essential components of the infectious prions is the most striking feature associated to these diseases. Additionally, different prion strains have been isolated from animal diseases despite the lack of DNA or RNA molecules. Mounting evidence suggests that prion-strain-specific features segregate with different PrP^Sc conformational and aggregation states.

Strains are of practical relevance in prion diseases as they can drastically differ in many aspects, such as incubation period, PrP^Sc biochemical profile (e.g., electrophoretic mobility and glycoform ratio) and distribution of brain lesions. Importantly, such different features are maintained after inoculation of a prion strain into genetically identical hosts and are relatively stable across serial passages.

This review focuses on the characterization of prion strains and on the wide range of important implications that the study of prion strains involves.

Keywords: :

• cellular prion protein (PrP^C)
• scrapie prion protein (PrP^Sc)
• transmissible spongiform encephalopathies (TSEs)
• prion strains
• strain mutation
• variant Creutzfeldt-Jakob Disease
• sporadic Creutzfeldt-Jakob Disease

Acknowledgments

We thank Dr Lisa Michelle Restelli for editing the manuscript. Table of contents graphic by Dr Elena Criscuolo.