02 February 2009

Prions, Viroids and Virusoids

Prions
Types of prions:
• Sheep version – scrapie (TSE)
• Cow version – mad cow (BSE- a type of TSE)
• Human version – Creutzfeldt-Jakob disease

A disease-causing agent that is neither bacterial nor fungal nor viral and contains no genetic material. A prion is a protein that occurs normally in a harmless form. By folding into an aberrant shape, the normal prion turns into a rogue agent. It then coopts other normal prions to become rogue prions.

• Prions are rogue protein that transform other cellular protein (PrPC) to the prion form PrPsc.
• PrPc gene on chromosome 20
• More and more PrPsc gets transformed until they completely clogg brain cells
• Cells misfire, work poorly or don’t work at all.
• Cells dir, release prions into blood stream to re-inact other cells
PrPC normally does membrane-anchored glycoprotein

Pathogenesis
• Spongiform encephalitis
• “sick” brains, riddled with holes
• Looks like swiss cheese


CLICK PICTURE FOR A LARGER VIEW! :D
http://www.nature.com/jidsp/journal/v7/n1/thumbs/5640076f5th.gif


CLICK PICTURE FOR A LARGER VIEW! :D
http://www.rkm.com.au/BSE/prionimages/PRIONS-600.jpg


CLICK PICTURE FOR A LARGER VIEW! :D
http://www.mol.biol.ethz.ch/groups/wuthrich_group/research/struc_pics/Mammalian_prions/image

Conversion of prions
• PrPsc forms a heterodimer with normal PrPc
• Template for altering the protein fold
• Tightly coiled α-helix converted to loose β-sheets

This picture illustrates the effect of prions on cells

CLICK PICTURE FOR A LARGER VIEW! :D

Transmission
• Eating contaminated beef or contaminated mutton
• Through blood transfusion

Viroids
• Viroids are infectious agents composed exclusively of a single piece of circular single stranded RNA which has some double-stranded regions
• Plants pathogen (25 main sequences identified)
• Hepatitis D virus that infects man has a structure similar to viroids

Mechanism of action
Viroids are suspected to be ribozymes (ribozymes are RNA molecules, hydrolyze their own phosphodiester bonds, or the hydrolysis of bonds in other RNAs, but they have also been found to catalyze the aminotransferase activity of the ribosome)

Disease caused by Viroids
• The only human disease known to be caused by a viroid-like entity is Hepatitis D
• Hepatitis D was previously ascribed to a defective virus called the delta agent
• There is extensive sequence complementarity between the hepatitis D viroid RNA and human liver cell 7S RNA
- The 7S RNA 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
• Co-infection with Hepatitis B virus.
• Bodily fluid
- Unprotected sex
- Sharing contaminated needles
- Close proximity


CLICK PICTURE FOR A LARGER VIEW! :D
http://www.clinical-virology.org/pages/cvn/sp_vr/viral_info/bbv/HTML/hep_d_big.jpg

Virusoid
Virusoid is an infectious agent that infects plants in conjunction with an assistant virus
• Viroids (circular RNA molecules that infect plants but don't require an assistant virus)

Properties
• Not considered a virus but a subviral particle
• The size and structure is similar to viroids
• Its genome is a single molecule of single stranded circular RNA that is several hundred nucleotides long and codes for nothing but its own stucture.