● $BlogItemTitle$> @ Monday, February 2, 2009 ●
Lecture 16!
1) Conventional view of infectious disease:
caused either by either viruses, bacteria, fungi or other parasites
2) Definition of prions
Prions are a disease-causing agent that is neither bacterial nor fungal nor viral and contains no genetic material.
A prion is a protein (PrPC) that occurs normally and harmlessly; but by folding into an aberrant shape, the normal prion turns into a rogue agent. It then corrupts other normal prions to become rogue prions.
More and more rogue proteins are produced until brain cells are completely clogged. Cells then start misfiring and functioning poorly or stops functioning; cells die and release prions into blood to re-infect other cells.
Prions have been held responsible for a number of degenerative brain diseases, including scrapie (a fatal disease of sheep and goats), mad cow disease and the Creutzfeldt-Jacob disease.
3) PRPC
= membrane-anchored glycoprotein
Its function has not been fully resolved but it is known that PRPC can bind copper (II) ions with high affinity. The significance of this is not clear, but it presumably relates to PrP structure or may have other important physiological roles. Features of the regulation of PrPc expression, cellular trafficking as well as copper uptake, protection against oxidative stress, cell adhesion, differentiation, signaling and cell survival are observed; so it is likely that PrPc plays pleiotropic roles in neuronal and non-neuronal cells, and as such the loss of function of PrPc may be an important component of various diseases.
4) Pathogenesis
= primary target of prions are the brain, causing brain damage and death
= spongiform encephalitis
= "sick" brains, riddled with holes
5) Conversion
= PrPSC forms a heterodimer with normal PrPC
= Template for altering protein fold.
= Tightly coiled alpha helix converted to loose beta sheets
6) Transmission
= Consumption of contaminated beef or mutton
= Blood transfusion
7) Viroids, mechanism of action, disease caused
- Infectious agents composed exclusively of a single piece of circular single-stranded RNA which has some double-stranded regions
- Plant pathogens (25 main sequences)
- Hepatitis D virus that infects man has a structure similar to viroids
= Mechanism of Action
- Viroids suspected to be ribozymes
- Ribozymes are RNA molecules that hydrolyze their own phosphodiester bonds, or other bonds in other RNA. They are also known to catalyze the aminotransferase activity of the ribosome.
= Disease caused
- The only human disease known to be caused by a viroid-like entity is Hepatitis D, which causes liver cell death via sequesteriung 7S RNA and/or cleaving it
- Hepatitis D previously ascribed to be a defective virus called the delta agent
- Extensive sequence complementarity between Hepatitis D viroid RNA and human liver cell 7S RNA. The structure is involved in the translocation of secretory and membrane-associated particles
8) Transmission of Hepatitis D
= Co-infection with Hepatitis B virus
= Bodily fluid
- Inprotected sex
- Sharing of contaminated needles
- Close proximity
9) Virusoid
= An infectious agent that infects plants in conjunction with an assistant virus, which is required for successful infection. Virusoids consist of single-stranded RNA.
-Viroids (circular RNA molecules that infect plants but do not require an assistant virus)
10) References
http://www.medterms.com/script/main/art.asp?articlekey=5047
http://en.wikipedia.org/wiki/PrPSc
http://knowledgerush.com/kr/encyclopedia/Virusoid/
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T36-45030WN-9&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=aca080b9d90a8afb2b8c9146aa61c52d