UNCONVENTIONAL VIRUSES/AGENTS/PRIONS

V.E. Gabriel, MD

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES(TSEs, TRANSMISSIBLE CEREBRAL AMYLOIDOSES,

PRIONDISEASES)

• 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

• Kuru

• Fatal Familial Insomnia (FFI)

• Creutzfeldt-Jakob disease (CJD)

• Scrapie

• Bovine Spongiform Encephalopathy (BSE)

• Chronic Wasting Disease (CWD)

Prion DiseasesPrion Diseases

HumanHuman AnimalAnimal

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.

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

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

ScrapieScrapie BSEBSE

CJDCJDKuruKuru

Microscopic changes

• 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

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.