PROFILE.


This blog is proudly run by two girls :

- Nur Rashilah &
- Tan Him Gee

of MB0801, Nanyang Polytechnic ;
School of Chemical & Life Sciences
:)


CONTENTS.

- Formal Welcome
- First Scoop To Virology
- Viral Replication Strategies
- Viral Replication Animation
- Viral Genetics
- Viroids & Prions
- Virusoids
- Baltimore Classification


CREDITS.

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Viroids and Prions.

Our topic of focus this time round will be on viroids and prions!

To start off, Viroids and Prions differ from viruses in many significant ways. Unlike viruses, viroids do not have protein capsids protecting their nucleic acid whereas prions do not contain nucleic acid like viruses do.


Viroids

•Viroids are fragments of RNA associated with plant and animal diseases

–May have originated as introns clipped from mRNA prior to translation

–May act as abnormal regulatory molecules

–Mode of replication not known

–Plant diseases = yellowing of leaves, stunted growth; potato spindle tuber disease, chrysanthemum stunt disease, cadang cadang, and others

–Animal diseases = slow virus diseases


Classification

•Avsunviroidae: e.g. avocado sunblotch viroid, peach latent mosaic viroid

•Pospiviroidae:

Subgroup 1: potato spindle tuber viroid, coconut cadang cadang viroid, tomato plant macho viroid

Subgroup 2: citrus bent leaf viroid, pear blister canker viroid


Replication

Circular, pathogenic RNAs are replicated by a rolling circle mechanism in vivo. There are two variations of this rolling circle mechanism:

In the first variation (A), the circular plus strand is copied by viroid RNA-dependent RNA polymerase to form a concatameric minus strand (step 2). Site-specific cleavage (arrows) of this strand produces a monomer that is circularized by a host RNA ligase (step 3) and then copied by the RNA polymerase to produce a concatameric plus strand. Cleavage of this strand (step 5) produces monomers which, on circularization, produces the progeny circular, plus RNA, the dominant form in vivo.

In the other variation (B), the concatameric minus strand of step 1 is not cleaved but is copied directly to give a concatameric plus strand (step 3), which is cleared specifically to monomers for ligation to the circular progeny. Those RNAs that self-cleave only in the plus strand in vitro are considered to follow this route.

Human pathologies induced by viroids

The only human disease known to be caused by a viroid is hepatitis D. This disease was previously ascribed 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.



Prions



•Prions are infectious protein particles representing an abnormal form of a natural brain protein named PrPc (Prion Protein cellular); PrPsc is the abnormal, disease-causing form (Sc for scrapies)

http://www.mad-cow.org/~tom/prion_dipoles.html

Prion Structure

The structure on the left is the normal PrP structure and consists of aplpha helices. The structure on the right is the PrPsc structure and consists of beta sheets. The PrPsc strucute can pair with the PrP strucuture and convert it into the scrapie form

http://www.uccs.edu/~rmelamed/MicroFall2002/Chapter%2010/Prion%20Structure.html

–Can arise from a mutation in the gene that codes for PrPc (30 different mutations identified) or by ingestion of prion-infected tissue; makes more of itself by changing PrPc into PrPsc

–May travel between cells in membranous bubbles called exosomes

–May replace protective proteins on brain cell membranes, killing the cells and giving the brain a spongy appearance – spongiform encephalopathy

–Loss of muscle control, dementia, wasting, paralysis, or death results from brain damage – normally in the brain stem

–Brain cells have can normally degrade defective proteins but have difficulty breaking down PrPsc as fast as it forms

Examples:

•Kuru
•Mad Cow Disease (bovine spongiform encephalopathy – BSE)
•Creutzfeldt-Jacob Disease (CJD)
•Scrapies


Pathology

•Diseases caused by prions are characterized as spongiform encephalopathies.

•Holes develop throughout the brain.

•Cells begin to die from the abnormal prions’ ability to link together and form long protein rods.

•The tissue damage causes progressive degeneration in neurological control that can affect things like balance, muscular control, mood, and sleep (depending upon the area of the brain most affected).

•All prion-caused diseases are fatal.


Replication

The prion is a product of a human gene, termed the PrP gene, found on chromosome 20. This gene contains two exons separated by a single intron. Exon I and Exon II are transcribed and the two RNAs ligated into a single mRNA. This mRNA contains an open reading frame (ORF) or protein coding region which is translated into the PrP protein. The PrP protein is a precursor of the prion protein. It is termed PrP 33-35.

The PrP 33-35 undergoes several post-translational events to become the prion protein (PrP 27-30):

1. Glycosylation - at two sites.

2. Formation of a disulfide bond between two cysteine residues.

3. Removal of the N-terminal signal peptide.

4. Removal of the C-terminal hydrophobic segment.

5. Addition of a phosphatidylinositol glycolipid at the C-terminal.

6. Removal of the N-terminal first 57 amino acids.

http://www.kcom.edu/faculty/chamberlain/Website/Lects/PRIONS.HTM

In normal cells only the PrP 33-35 protein is synthesized. It is found in the neural cell membrane where it's function is to sequester Cu++ ions. In abnormal ("infected") cells, the PrP 27-30 is produced from the PrP 33-35 protein. The PrP 27-30 triggers a series of reactions that produce more PrP 27-30 proteins, i.e., PrP 27-30 induces its own synthesis. In addition to the post translational modifications, the PrP 27-30 protein differs from the PrP 33-35 protein in a single amino acid residue. Residue 178 in the PrP 27-30 contains an asparagine residue whereas the PrP 33-35 protein has an aspartate residue at this position. This causes a conformational change in the PrP 27-30 protein from an alpha-helix to a beta -sheet.

This conformational change in the PrP 27-30 protein has three effects:

1. It imparts to the PrP 27-30 protein the ability to induce the same alpha-helix to beta-sheet conformation in the PrP 33-35 protein. This is a permanent conformational change. It thus induces its own "replication."

2. The beta-sheet-forming peptides aggregate to form amyloid fibrils.

& with that, we conclude this topic on Viroids and Prions. Hope you guys learn something new from it! =)