Originally Posted on Landes Bioscience | April 2010
Prions are self-propagating proteinaceous infectious agents capable of transmitting disease in the absence of nucleic acids. The nature of the infectious agent in prion diseases has been at the center of passionate debate for the past 30 years. However, recent reports on the in vitro generation of prions have settled all doubts that the misfolded prion protein (PrPSc) is the key component in propagating infectivity.
However, we still do not understand completely the mechanism of prion replication and whether or not other cellular factors besides PrPSc are required for infectivity. In this article, we discuss these recent reports under the context of the protein-only hypothesis and their implications.
Prions are self-propagating particles of proteinaceous origin which share the ability to transmit disease with typical infectious organisms such as viruses and bacteria, but in contrast to them, prions do not have genetic material. Prion diseases have been found in humans and other mammals, including cattle, sheep, cervids, felines and rodents.
In addition to be transmitted by infection, the disease can have inherited and sporadic origins. In the transmissible cases, infection of the host is preceded by a variable incubation period and followed by the appearance of clinical symptoms. Prion diseases are 100% fatal and after a long pre-symptomatic period in which the agent is slowly replicating, the clinical phase is often very rapid, progressive and severe.
Although the exact molecular nature of prions is not completely clear, it is widely accepted in the field that the prion protein (denoted PrP) in its infectious conformation (PrPSc) is the main or perhaps only component of the infectious agent. Having a misfolded protein as an infectious agent makes prions very unconventional. Even if some co-factors are proven to be required, the minimal infectious agent should be much less complex than a virus or any other form of conventional micro-organism.
Given the heretical nature of prions, the “protein-only” hypothesis has remained controversial for decades. Recent reports demonstrating the formation of highly infectious prions completely in vitro have provided the strongest proof for the prion hypothesis and have taken the field to an entirely new position.