1. Rabies virus and Prion Dongli Pan
Department of Medical Microbiology and Parasitology
Zhejiang University School of Medicine

2. Rabies virus
Member of the Lyssavirus of the Rhabdoviridae

3. Baltimore classification
DNA viruses
RNA viruses
Baltimore classification
Fields Virology, 6th edition

4. 1. Biological properties
Has a cylindrical morphology
-ssRNA enveloped virus
capsid has helical symmetry
Is a neurotropic virus

5. Negri body
内基小体
Forms round or oval acidophilic cytoplasmic inclusion bodies.
Negri body in the cytoplasm of infected neuron

6. Rabies
Transmission
– by the bite of a rabid animal (commonly a dog or a cat)
– the contamination of scratch wounds by virus- infected saliva.
Clinical findings
Incubation/prodromal period 1 to 3 months
CNS infection
Hydrophobia. This fear of water is the result of the pain associated with drinking.
Seizures and hallucinations.
Paralysis may lead to respiratory failure.
Coma
Mortality is >99%. Most deadly virus!

7. Pathogenesis

8. Laboratory diagnosis
Animals: Animals in a rabies endemic area should beheld for 10 days for observation. If the animal is sick, kill the animal and collect samples from hippocampus tissues and look for 1) Negri bodies 2) viral antigens by immunofluorescence
Human: Collect samples of saliva, serum, spinal fluid, and skin biopsies and perform RT-PCR or immunofluorescence.
海马回

9. Postexposure rabies prophylaxis
Long incubation period is the basis of postexposure prophylaxis
Local wound care
Cleanse wound with soap and water. Sterilize with ethanol or iodine.
Combination of passive and active immunization:
Passive immunization with rabies antiserum (HRIG,given the day before or on the day of active immunization）
Active immunization with antirabies vaccine (HDCV, im given on days 0, 3, 7, 14, 28).

10. From BSE to Prion
Prion: An infectious proteinaceous particle of nonnucleic acid composition

11. Bovine spongiform encephalopathy (BSE)
mad-cow disease

12. Prion protein (PrP): from PrPC to PrPSc
Same amino acid sequences but different structures
PrPSc (scrapie prion protein)
43% β- sheet and 30% α-helix
Insoluble
Resistant to protease K
Pathogenic
PrPC (cellular prion protein)
Mainly α-helix
Soluble
Sensitive to protease K
Has normal functions, not pathogenic

13. Prions aggregate extracellularly within the central nervous system to form plaques known as amyloid, which disrupt the normal tissue structure
Strong resistance to autoclave, UV, regular disinfectants.
Standard autoclave (121oC, 20 min) does not inactivate it. Needs 134oC, 2h

14. Transmissible Spongiform Encephalopathies (Prion Diseases)
• Human
– Kuru disease
– Creutzfeldt--Jacob disease (CJD)
– variant Creutzfeldt--Jacob disease (vCJD)
• Animals
– Scrapie of sheep and goats
– Bovine spongiform encephalopathy (BSE, mad cow)
Progressive neurodegenerative disease

15. The characteristics of Prion diseases
normal

16. Diagnosis and Prevention
Immunoblotting assay (Western blot): Treat tissue with proteinase K to digest PrPC, and then analyze with Western blot for the presence of PrPSc
Immunohistochemstry: Also treat with proteinase K first
Genetic analysis: For inherited mutations in the PrP gene.
Prevention: quarantine of animals and complete disinfection of medical devices. No treatment.