39. unconventional viruses
TRANSCRIPT
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UNCONVENTIONAL VIRUSES/AGENTS/PRIONS
V.E. Gabriel, MD
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TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES(TSEs, TRANSMISSIBLE CEREBRAL AMYLOIDOSES,
PRIONDISEASES)
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• Stanley B. Prusiner coined the term proin from Proteinaceous infective particle
and changed to prion to sound it rhythmic.
• Prion diseases were caused by misfolded proteins.
• Elucidated the gene and mechanism by which wild type protein
bring about the
clinical disease.
INTRODUCTION
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• Kuru
• Fatal Familial Insomnia (FFI)
• Creutzfeldt-Jakob disease (CJD)
• Scrapie
• Bovine Spongiform Encephalopathy (BSE)
• Chronic Wasting Disease (CWD)
Prion DiseasesPrion Diseases
HumanHuman AnimalAnimal
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Classification of prion diseasesClassification of prion diseases• Infectious/ExogenousInfectious/Exogenous
– e.g., Kuru, BSE (mad cow disease), Scrapie– Spread by
• Consumption of infected material.• Transfusion.
• SporadicSporadic
• Familial/HereditaryFamilial/Hereditary– Due to autosomal dominant mutation of PrP.
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Differences between cellular and scrapie proteinsDifferences between cellular and scrapie proteinsPrPPrPCC PrPPrPSCSC
SolubilitySoluble Non soluble
Structure Alpha-helical Beta-sheeted
Multimerisation state Monomeric Multimeric
InfectivityNon infectious Infectious
Susceptibility to Proteinase KSusceptible Resistant
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Gross and Microscopic Changes Gross and Microscopic Changes
Grossly there is Cortical atrophy and Grossly there is Cortical atrophy and ventricular ventricular
dilatation may also be present.dilatation may also be present.
Gross changes
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ScrapieScrapie BSEBSE
CJDCJDKuruKuru
Microscopic changes
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• Gliosis within plaques.
• Loss of oligodendrocytes within plaques.
• Axons usually remain intact in plaques.
• Both CD4+ and CD8+ lymphocytes are present
in active
lesions.
Other microscopic changesOther microscopic changes
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Diagnosis can be made by:
1. Clinical signs and Symptoms.
2. Detection of Scrapie
Associated fibrils.
3. Detection of Abnormal Prion protein (PrPsc) by Western blotting.
4. Two dimensional Gel Electrophoresis. 5.
Imunodiagnosis of Prion disease.6. Bioassay in Mice.
Diagnosis Diagnosis
Scrapie Associated fibrils.
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