An Overview of Biological Basics - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 28

deliver it selectively to a particular cell type. Thus, viruses can do great harm but can also be
important biotechnological tools.
2.1.4. Prions
A prion is an infectious agent composed of protein in a misfolded form. This is in contrast
to all other known infectious agents that must contain nucleic acids (either DNA, RNA, or
both). The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived
from the words protein and infection. Prions are responsible for the transmissible spongiform
encephalopathies in a variety of mammals, including bovine spongiform encephalopathy
(also known as “mad cow disease”) in cattle and Creutzfeldt e Jakob disease in humans.
All known prion diseases affect the structure of the brain or other neural tissue and all are
currently untreatable and universally fatal.
Prions propagate by transmitting a misfolded protein state. When a prion enters
a healthy organism, it induces existing, properly folded proteins to convert into the
disease-associated, prion form; the prion acts as a template to guide the misfolding of
more protein into prion form. The newly formed prions can continue to convert more
proteins themselves; this triggers a chain reaction that produces large amounts of the prion
form. All known prions induce the formation of an amyloid fold, in which the protein
polymerizes into an aggregate consisting of tightly packed beta sheets. Amyloid aggre-
gates are fibrils, growing at their ends, and replicating when breakage causes two growing
ends to become four growing ends. The incubation period of prion diseases is determined
by prion replication, which is a balance between the individual prior aggregate growth and
the breakage of aggregates. Note that the propagation of the prion depends on the pres-
ence of normally folded protein in which the prion can induce misfolding, animals which
do not express the normal form of the prion protein cannot develop or transmit the
disease.
This altered structure is extremely stable and accumulates in infected tissue, causing
tissue damage and cell death. This structural stability means that prions are resistant to
denaturation by chemical and physical agents, making disposal and containment of
these particles difficult. Prions come in different strains, each with a slightly different
structure, and most of the time, strains breed true. Prion replication is nevertheless
subject to occasional epimutation and then natural selection just like other forms of
replication. However, the number of possible distinct prion strains is likely far smaller
than the number of possible DNA sequences, so evolution takes place within a limited
space.
All known mammalian prion diseases are caused by the so-called prion protein, PrP. The
endogenous, properly folded, form is denoted PrP C (for common or cellular) while the
disease-linked, misfolded form is denoted PrP Sc (for scrapie, after one of the diseases first
linked to prions and neurodegeneration, that occurs in sheep.) The precise structure of the
prion is not known, though they can be formed by combining PrP C , polyadenylic acid,
and lipids in a Protein Misfolding Cyclic Amplification reaction.
Proteins showing prion-type behavior are also found in some fungi (e.g. Saccharomyces cer-
evisiae and Podospora anserine), which has been useful in helping to understand mammalian
prions. Interestingly, fungal prions do not appear to cause disease in their hosts.