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PAST STUDENT WEBPAGES on PRIONS
(w/corrections)

Student Web Pages

Priya Jayachandran, Hilary Faust, H&V 2005
http://www.stanford.edu/group/virus/prion/2005priya/links.html

Monique Anderson, Humans and Viruses 2004
http://www.stanford.edu/group/virus/prion/2004anderson/index.html

Cindy Lin, Humans and Viruses 2002
http://www.stanford.edu/~cinders8/prions2002.html
(Page cannot be found.)

Erica Chung and Carmen Holmes, Humans and Viruses 2000
http://www.stanford.edu/group/virus/prion/2000/prions.html
(Page cannot be found.)

John Mumm, Humans and Viruses 1999
http://www.stanford.edu/group/virus/prion/prion2.html

 

Corrections

Humans and Viruses 1999
http://www.stanford.edu/group/virus/prion/prion2.html


It has not yet been established if scrapie prions transferred into cattle brains can initiate infection….
It is still unknown whether or not scrapie, initially implicated in CJD, or BSE prion can cause disease in humans
,
although two farmers with BSE afflicted cattle have died of CJD in 1993.”

The first human case of vCJD was documented in 1996 in the UK, and since then, strong evidence that the outbreak that resulted and about 200 other human cases of vCJD are linked to the BSE prion.

Source: CDC. (2007). Prevention of Specific Infectious Diseases. CDC Travelers’ Health: Yellow Book. http://wwwn.cdc.gov/travel/yellowBookCh4-VariantPrions.aspx

 

“The kinetics of these associations predict the interactions are not cooperative, this is to say that the misfolded
prion protein does not actively recruit other misfolded prion gene products for form multimers. The data seems rather to define a slow process by which the occasionally misfolded prion protein will exist in the cell for an extended period of time, after which another randomly misfolded prion protein will associate with the first. Subsequently, as multimers of the misfolded prion proteins associate, they have a greater statistical chance of associating with other misfolded prion proteins. It is unknown as to whether or not the large oligomers of the misfolded prion can promote misfolding of normally expressed prion products. Although there is no evidence yet for this activity, it is still an attractive hypothesis”.

Although the precise method that PrP(sc) causes Prp(c) to change conformation is unknown, nucleated PrP(sc) have been shown to induce misfolding of PrP(c).

Source: Soto, Claudio. Prions: The New Biology of Proteins. Boca Raton, FL: Taylor & Francis, 2006

.

Humans and Viruses 2004
http://www.stanford.edu/group/virus/prion/2004anderson/index.html


Under Prion Diseases: All the TSEs are characterized by neuronal loss, accompanied by amyloid
plaques or fibril formation after spongiform degeneration of brain tissue.
They are progressive neuronal diseases that are always fatal.”

The pathology of GSS includes the formation of multicentric PrP amyloid plaques, Kuru has “florid” plaques, and vCJD shows a much higher concentration of amyloid plaques than sCJD and fCJD.

Source: Collinge, John. (2001). Prion diseases of humans and animals: Their causes and molecular basis. Annual Review of Neuroscience 24: 519-50.



Under Outcomes: Once symptoms appear, death results in 6 months -1 year. There is no cure and our own
bodies can't even mount an immune response to this pathogen
.”

Sporadic CJD can result in death as quickly as 2-3 months from the onset of symptoms. 70% of sCJD patients die within 6 months of onset.

Also, to clarify, the reason why our bodies cannot mount an immune response is because PrPc and PrPsc have the same epitopes and our bodies recognize the PrPc epitopes as “self.”

Sources:
Collinge, John. (2001). Prion diseases of humans and animals: Their causes and molecular basis. Annual Review of Neuroscience 24: 519-50.
Fields Virology, 5th ed. (2007).

Under Epidemiology: “Pretty much all of the human TSEs occur throughout the population at an
equal frequency,
but Kuru was endemic among the Fore People of New Guinea until the ritualistic practice of cannibalism
was ended there. Also CJD tends to occur in older populations with very few cases
occuring in individuals under the age of 40.”

While prevalence of inherited and sporadic human prion diseases is relatively uniform worldwide, acquired prion diseases are not equally distributed around the world. According to the US CDC,between 1995-2006, a total of 195 human cases of vCJD were reported worldwide, 162 in the UK, 20 in France, 4 in Ireland, 2 in the United States (US), and 1 each in Canada, Italy, Japan, the Netherlands, Portugal, Saudi Arabia and Spain.

Referring to the age range of over 40, the primary age group affected depends on the type of CJD. Sporadic CJD does usually hit between the ages of 45-75 (peak between 60-65 years), but vCJD ranges from 16-51 years, with the median age of death being 28. 

Sources:
Collinge, John. (2001). Prion diseases of humans and animals: Their causes and molecular basis. Annual Review of Neuroscience 24: 519-50.
CDC. (2007). Prevention of Specific Infectious Diseases. CDC Travelers’ Health: Yellow Book. http://wwwn.cdc.gov/travel/yellowBookCh4-VariantPrions.aspx



“Presently there is no real treatment for any of the TSEs.”

This is mostly true. I just wanted to  bring to light that a controlled trial testing safety and activity of quinacrine (Mepacrine hydrochloride) to treat human prion disease began recruiting patients with any prion disease in 2004 in the UK. Quinacrine is able to reduce the protease resistance of PrPsc, and it was shown in vitro that it inhibits conversion of PrPc to PrPsc. In murine models, quinacrine slowed the development of fibrillogenic prion protein and PrPsc accumulation in ScN2a cells.

Sources:
UK Medical Research Council Clinical Trials Unit. (2006). Prion-1: Randomised trial of quinacrine in human prion disease. http://www.ctu.mrc.ac.uk/studies/cjd.asp
Barret, F. Tagliavini, G. Forloni, C. Bate, M. Salmona, L. Colombo, A. De Luigi, L. Limido, S. Suardi, G. Rossi, F. Auvré, K. T. Adjou, N. Salès, A. Williams, C. Lasmézas, and J. P. Deslys. (2003). Evaluation of Quinacrine Treatment for Prion Diseases. Journal of Virology 77(15): 8462-8469.

 

Humans & Viruses 2005
http://www.stanford.edu/group/virus/prion/2005priya/links.html


Under Prion Profile, “Human Diseases listed only include Kuru, CJD, and vCJD.”

Should include Gerstmann-Straussler-Scheinker disease (GSS), Fatal Familial Insomnia (FFI), Sporadic Fatal Insomnia (SFI), and the various other forms of CJD including Sporadic CJD (sCJD) and Familial CJD (fCJD).

Source: Fields Virology, 5th ed. (2007).

In the epidemiology portion, “vCJD has emerged in England and spread worldwide through beef trade,
Kuru has been focused among the Fore of Papua New Guinea”

The epidemiology of GSS, FFI, sCJD, and fCJD are not mentioned; these inherited and sporadic prion diseases have uniform distribution and prevalence worldwide. vCJD has also not spread “worldwide;” it’s mostly a disease of developed nations. From 1995 through mid August 2006, a total of 195 human cases of vCJD were reported, 162 in the UK, 20 in France, 4 in Ireland, 2 in the United States (US), and 1 each in Canada, Italy, Japan, the Netherlands, Portugal, Saudi Arabia and Spain. It has not spread to Asian countries other than Japan nor Africa.

Source: CDC. (2007). Prevention of Specific Infectious Diseases. CDC Travelers’ Health: Yellow Book. http://wwwn.cdc.gov/travel/yellowBookCh4-VariantPrions.aspx

 

“There are three types of prion diseases: spontaneous, acquired and genetic. The cause for spontaneous is unknown.
Acquired is caused by, in humans, ingestion of infected tissue.

sCJD is also caused by iatrogenic methods or contaminated human growth hormone isolated from cadaveric pituitaries prior to 1985.

Source: Fields Virology, 5th ed. (2007).

If the PrP gene mutates it can cause genetically inherited disease. There are 20 mutations that can cause these diseases and 5 are significantly genetically linked. The mutations have been found all through the protein; there is not just one area that mutates to cause prion diseases.”

Over 20 mutations have been discovered that are linked to familial prion disease. Numbers found in peer-reviewed literature vary, but one article stated that at least 56 mutations are known.

Sources:
Collinge, John. (2001). Prion diseases of humans and animals: Their causes and molecular basis. Annual Review of Neuroscience 24: 519-50.

Manuela Pastore, Steven S. Chin, Karen L. Bell, Zhiqian Dong, Qiwei Yang, Lizhu Yang, Jue Yuan, Shu G. Chen, Pierluigi Gambetti, and Wen-Quan Zou. (2005). Creutzfeldt-Jakob Disease (CJD) with a Mutation at Codon 148 of Prion Protein Gene. Am J Pathol 167(6): 1729-38.

 

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