Prions, Viriods and Virusoids

Prions, Viriods and Virusoids

Prions

Prions are anomalous infectious pathogens that cause a group of constantly fatal neurodegenerative diseases mediated by an entirely contemporary mechanism. Prion diseases may present as genetic, infectious, or sporadic disarrays, all of which involve variation of the prion protein (PrP), a essential of normal mammalian cells. CJD generally presents as progressive dementia, whereas scrapie of sheep and bovine spongiform encephalopathy (BSE) are generally apparent as ataxic illnesses.


Prions are devoid of nucleic acid and seem to be composed exclusively of a modified isoform of PrP designated PrPSc.‡ The normal, cellular PrP, denoted PrPC, is converted into PrPSc through a process whereby a portion of its α-helical and coil structure is refolded into β-sheet (25). This structural transition is accompanied by profound changes in the physicochemical properties of the PrP. The amino acid sequence of PrPSc corresponds to that encoded by the PrP gene of the mammalian host in which it last replicated. In contrast to pathogens with a nucleic acid genome that encode strain-specific properties in genes, prions encipher these properties in the tertiary structure of PrPSc (26–Transgenetic studies argue that PrPSc acts as a template upon which PrPC is refolded into a nascent PrPSc molecule through a process facilitated by another protein.

More than 20 mutations of the PrP gene are now known to cause the inherited human prion diseases, and significant genetic linkage has been established for five of these mutations (4, 16, 29–The prion concept readily explains how a disease can be manifest as a heritable as well as an infectious illness.

One good example of a disease under Prions is Scrapie, which is a fatal, depraving disease that affects the central nervous system of sheep and goats. The transmission of scrapie is mainly due to the unhygienic way of feeding unhealthy or infected food through unlawful methods to the animals. In such cases, infected animals with scrapie such as those dead sheeps made into products were fed to living cows that are reared by farmers, preparing to slaughter them for meat. Another example of Prions disease is the Mad cow disease, also known as BSE, a type of TSE but slight genetically differences.

Shown in the picture above, small vacuoles
are symptoms of prions active in the brain tissues.

Humans are also susceptible to several prion diseases:

• CJD: Creutzfeld-Jacob Disease
• GSS: Gerstmann-Straussler-Scheinker syndrome
• FFI: Fatal familial Insomnia
• Kuru
• Alpers Syndrome

These original classifications were based on a clinical evaluation of a patients family history symptoms and are still widely used, however more recent and accurate molecular diagnosis of the disease is gradually taking the place of this classification.
The incidence of sporadic CJD is about 1 per million per year.GSS occurs at about 2% of the rate of CJD.

It is estimated that 1 in 10,000 people are infected with CJD at the time of death.These figures are likely to be underestimates since prion diseases may be misdiagnosed as other neurological disorders.

The diseases are characterised by loss of motor control, dementia, paralysis wasting and eventually death, typically following pneumonia. Fatal Familial Insomnia presents with an untreatable insomnia and dysautonomia. Details of pathogenesis are largely unknown.
Visible end results at post-mortem are non-inflammatory lesions, vacuoles, amyloid protein deposits and astrogliosis.

GSS is distinct from CJD, it occurs typically in the 4th-5th decade, characterised by cerebellar ataxia and concomitant motor problems, dementia less common and disease course lasts several years to death. Originally, it is thought to be familial, but now known to occur sporadically as well.

CJD typically occurs a decade later has cerebral involvement so dementia is more common and patient seldom survives a year, which is originally thought to be sporadic, but now known to be familial as well.

FFI pathology is characterised by severe selective atrophy of the thalamus.

Alpers syndrome is the name given to prion diseases in infants.

Scrapie was the first example of this type of disease to be noticed and has been known about for many hundreds of years. There are two possible methods of transmission in sheep:

1. Infection of pasture with placental tissue carrying the agent followed by ingestion,or direct sheep-lamb transmission i.e. an acquired infection.
2. Parry showed considerable foresight by suggesting that it is not normally an infectious disease at all but a genetic disorder. He further suggested that selective breeding would get rid of the disease.

Humans might be infected by prions in 2 ways:

1. Acquired infection (diet and following medical procedures such as surgery, growth hormone injections, corneal transplants) i.e. infectious agent implicated.
2. Apparent hereditary mendelian transmission where it is an autosomal and dominant trait. This is not prima facie consistent with an infectious agent.

This is one of the features that single out prion diseases for particular attention. They are both infectious and hereditary diseases. They are also sporadic, in the sense that there are also cases in which there is no known risk factor although it seems likely that infection was acquired in one of the two ways listed above.

Kuru is the condition which first brought prion diseases to prominence in the 1950s. Found in geographically isolated tribes in the Fore highlands of New Guinea. Established that ingesting brain tissue of dead relatives for religious reasons was likely to be the route of transmission. They ground up the brain into a pale grey soup, heated it and ate it. Clinically, the disease resembles CJD. Other tribes in the vicinity with same religious habit did not develop the disease. It is speculated that at some point in the past a tribe member developed CJD, and as brain tissue is highly infectious this allowed the disease to spread. Afflicted tribes were encouraged not to ingest brain tissue and the incidence of disease rapidly declined and is now almost unknown.

Viroids

Viroids are plant pathogens that consist of a short stretch of highly complementary, circular, single-stranded RNA without the protein coat that is typical for viruses. The genome of the smallest known viruses capable of causing an infection by themselves is around 2 kilobases in size. The human pathogen hepatitis D is similar to viroids.

Because of their simplified structures both prions and viroids are sometimes called subviral particles. Viroids mainly cause plant diseases but have recently been reported to cause a human disease.

The only human disease known to be caused by a viroid is hepatitis D. This disease was previously imputed to a defective virus called the delta agent. However, it now is known that the delta agent is a viroid enclosed in a hepatitis B virus capsid. For hepatitis D to occur there must be simultaneous infection of a cell with both the hepatitis B virus and the hepatitis D viroid. There is extensive sequence complementarity between the hepatitis D viroid RNA and human liver cell 7S RNA, a small cytoplasmic RNA that is a component of the signal recognition particle, the structure involved in the translocation of secretory and membrane-associated particles. The hepatitis D viroid causes liver cell death via sequestering this 7S RNA and/or cleaving it.

Transmission
The hepatitis D viroid can only enter a human liver cell if it is enclosed in a capsid that contains a binding protein. It obtains this from the hepatitis B virus. The delta agent then enters the blood stream and can be transmitted via blood or serum transfusions.

Virusoid
Virusoids are circular single-stranded RNAs dependent on plant viruses for replication and encapsidation. The genome of virusoids consists of several hundred nucleotides and only encodes structural proteins.
Virusoids are similar to viroids in size, structure and means of replication

Summary of Prions, Viriods and Virusoids
Viroids, virusoids and prions are unusual infectious agents characterised by having a very small genome and in the case of prions, possibly no genome at all.
Viroids are common plant pathogens which are a serious economic problem. 25 different viroid sequences have been determined and numerous variants identified :

Pospiviroidae are a large group, only 2 members of the Avsunviroidae are currently known. The RNA genomes of viroids are 246-375 nucleotides in length and share many similarities:

• They are all single stranded covalent circles
• There is extensive intramolecular base pairing
• A DNA-directed RNA polymerase makes both plus and minus strands
• Replication does not depend on the presence of a helper virus
• No proteins are encoded

Reference
http://en.wikipedia.org/wiki/Prions
http://www.microbiologybytes.com/virology/Prions.html
http://www.microbiologybytes.com/virology/Viroids.html
http://en.wikipedia.org/wiki/Viroids
http://en.wikipedia.org/wiki/Virusoid
http://www.rkm.com.au/
http://www.pandasthumb.org/
http://www.ens-newswire.com/ens/jul2006/20060710_prions.gif