Genaral characteristic of Prions

1. Prions
Dr. R. S. Jadhav
Department of Microbiology,
VNBN Mahavidyalaya, Shirala, Dist- Sangli.

2. Introduction
 In 1960s, Alper and Griffith developed the hypothesis that the transmissible spongiform
encephalopathies (TSEs) are caused by an infectiouse agent consisting solely of proteins.
In 1982 American scientist Stanley B. Prusiner isolated and purified the infectious agent
as protein.
 He coined the term prion for infectious agent by combining first letters of the words
proteinaceous and infectious and on to make analogy to virion. In 1997, Prussiner was
awarded the Nobel prize in medicine and physiology.
 Prions are infectious protein particles responsible for fatal neurodegenerative diseases in
humans and animals. Prion diseases are often called transmissible spongiform
encephalopathies because of the appearance holes in the brain tissue. Destruction of brain
tissue gives spongy appearance.
 Characteristics of Prions
 Prions are infectious glycoproteins.
 They don’t contains DNA, RNA or capsid.
 Prions cause TSEs (neurodegenarative diseases) in which large vacuoles in the
brain tissues are produced.
 Prion have not been visualized but assayed for infectevity in mouse by
intracerebral inoculation route. Mice develop clinical symptoms several months
later.
 Infectivity is not destroyed by UV rays or nucleases. They can be destroyed by
chemicals that denature protein and heat.

3.  Normal neuronal cells have normal cellular protein known as PrPc (c for cellular), on their cell
surface.
 The modified form of PrPsc is known as prion PrPc (Prp-protease resistant protein and sc- for
scrapie).
 Prion protein converts normal host protein to prion protein that fold abnormally. All known
prions induce the formation of an amyloidal fold, in which the prions bind to form aggregate
consisting of tightly packed beta sheets. The aggregates damage brain tissue forming large
vacuoles.
 Prion cause slow infection. The incubation period ranges from one to several years. This
diseases are transmitted directly from one person to another, indirectly from fomites and by
ingestion of contaminated meat. Human and animal diseases caused by prion are given in table.
Diseases Host Symptoms
Scrapie Sheep &
goat
Animals scrape off their fleece (wool coat) against rocks or
trees due to itching sensation
Transmissible mink encephalophathy
(TME)
Mink Behavioral changes such as confusion, loss of cleanliness and
aimless circling
Chronic wasting diseases (CWD) Mule dear,
elk
Behavioral changes like lowering of the head and repetitive
walking in set patterns
Bovin spongiform encephalophathy
(BSE) or Mad cow diseases
Cow Degeneration of physical and mental abilities and ultimately
death.
Creutzfeld-Jacob diseases (CJD) Human Dementia, leading to memory loss, hallucination and physical
problems
Kuru Human Laughing sickness and trembling with fear
Gerstmann-Straussler-Scheinker
syndrome (GSS)
Human Dysarthria(difficulty speaking) cerebellar ataxia (unsteadiness)
and dementia
Fetal familial Insomnia (FFI) Human Panic attacks,phobias, Hallucinations, inability to sleep &
dementia

4.  Some common symptoms of TSEs are loss of muscle coordination which leads to a
difficulty in walking, dementia characterized initially by loss of memory, diminished
intellect and poor judgement, progressive insomnia (inability to sleep), progressive tonic
paralysis and death.
 Diagnostic tests include: biopsy of brain tissue, immunofluorescence test on tonsilar
biopsies (prion protein accumulated in the tonsils), western blot and capillary
electrophoresis with laser- induced fluorescence detects prion in very small amount of
sample.
 Structure of Prion: The normal PrPc protein contains 253 amino acids. It undergoes post
translational modification. It undergose glycosylation at two sites Asp 181 and Asp 197.
There is formation of a disulfide bond between two cysteine residues. Signal peptide (1-
22 amino acids) is removed from N-terminus and hydrophobic segment (peptide 232-253)
is removed from C- terminus. A phosphatidylinositol anchor is added at the C- terminus.
Properties of PrPc and PrPsc are given below.,
 PrPc (Normal cellular protein)
 PrPc is a normal cellular protein found at the surface of neurons.
 It is a transmembrane glycoprotein.
 Its secondary structure contains 43% alpha helical and
3% beta –pleated sheet.
 It is easily soluble and easily degraded by proteases.
 It is encoded by a gene designated (in humans) PRNP located on human chromosome 20.

5. PrPsc (Protease resistant protein for scrapie):
 It is an abnormal, disease producing protein.
 PrPsc is a prion protein for scrapie.
 Its amino acid sequence is same as that of normal protein. Its conformation is changed.
 Its secondary structure contains 30% alpha helical and 43% beta pleated sheet.
 It is insoluble in many solvent and protease resistant protein.
 When PrPsc come in contact with PrPc on the cell surface converting PrPc to PrPsc.
Prion proteins induce the formation of an amyloidal fold.