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Prions: Current Papers?

Mike Poidinger mikep at biosci.uq.oz.au
Thu Feb 15 18:30:03 EST 1996

On 15 Feb 1996 08:06:28 GMT, burris at myna.com wrote:

>Does anyone know of any recent journal article titles concerning prion research and their implication
> in CJD, Kuru, scrapie or 
>other diseases?

Sure do.

>Some Questions to Ponder:
>Evidence suggests that prions do not contain nucleic acid since there is >>NO<<  concomitant 
>loss of infectiousness with nuclease treatment. If true, what evidence exists to 
>confirm or refute the protein, glycoprotein or lipoprotein based nature of the agent?

1) Recent articles in nature have shown that uninfectious, normal PrPc
(the protein in question) can be converted to infectious PrPsc in
vitro. They have also shown different strains of PrPsc can be produced
in vitro.
2) Transgenic animals with abnormal PrP genes spontaneously come down
with prion disease, 
3) The most accurate methods available fail to detect any kind of
genomic NA

THis is an incredibly short summary of 10 years of research.  All of
it avaliable on Medline.

>If prions are solely based on protein, glycoprotein or lipoprotein, or any combuination 
>there of, shouldn't a lability or alteration in the 3-D conformation of the agent's protein 
>based structure be expected when the agent is exposed to heat? 

Umm... why, exactly?  some proteins are heat labile, others are not.
RNAse and Thermostable polymerases spring to mind.

>Would not protease treatment also be expected to affect the infectiousness of the agent? 
>Some reports suggest that heat and 
>protease treatment does not reduce or eliminate the infective nature of the agent. How can this be explained based on the 
>above hypothesis?

The infectious agent is succeptible to proteinase K treatment.  It is
resistant to PARTIAL treatment under moderate conditions with this
enzyme.  Its uninfectious form, PrPc is sensitive to partial
proteolysis and in fact this is the major method of detection of
infectious vs uninfectious material.

>If prion replication is accomplished by the reverse translation of protein to mRNA shouldn't we be able to detect prion associated 
>mRNA in infected neurological tissue? What evidence suggests that reverse translation of protein is the actual mode of 
>replication used by prions? 

None at all.  This is a competely bogus hypothesis with no evidence.
BTW, since the infectious form of the protein is derived from a
naturally expressed host encoded protein, you actually find mRNA for
PrP in the neurolgical tissue of animals as a matter f course.

>I welcome your comments and ideas.
>Burris Ormsby, Professor Microbiology, Sheridan College, Canada

You asked a lot of broad-sweeping questions which cannot be answered
well in email of news format.  Look up some references with the name
'Prusiner, SB" in them.


Dr Mike Poidinger        Animal Welfare, NOT Animal Rights
Microbiology, UQ       
Australia                'Reality' is the only word in the english language
mikep at biosci.uq.oz.au    that should always be used in quotes

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