Virus Penyebab Infeksi Sistem Saraf

dr. Rahmiati
rahmilao76@gmail.com
Bagian Mikrobiologi Fakultas Kedokteran
Universitas Lambung Mangkurat
How Pathogens
• Skull orInvade CNS
backbone fractures
• Medical procedures
• Along peripheral nerves
• Blood or lymph
• Encephalitis: Inflammation of the brain.
Cerebrospinal Fluid

Cerebrospinal fluid is a clear,

colorless, and sterile fluid
Volume 90 -150 mL
 How Now Mad Cow?

Introduction to Prion Disease and Function

SHP – Neurobiology of Development

and Disease
TSE: Transmissible spongiform
encephalopathies
Prion-Related Diseases, Hosts, and Mechanism of Transmission

Pathophysiology Disease Host Mechanism

Kuru Human Cannibalism

Characteristics: Spontaneous PrP
C
to PrP
Sc
conversion or somatic
Sporadic CJD Human mutation
Infection from prion-containing material, eg, dura mater,

• Brain vacuolation Iatrogenic CJD Human electrode

Familial CJD Human Mutations in the PrP gene

• Astrogliosis nvCJD Human Infection from BSE

• Neuronal apoptosis GSS Human Mutations in the PrP gene

•
D178N mutation in the PrP gene, with M129
Accumulation of FFI Human polymorphism
C Sc
Sporadic fatal Spontaneous PrP to PrP conversion or somatic
misfolded prion insomnia Human mutation

plaques. Scrapie Sheep Infection in susceptible sheep

BSE Cattle Infection from contaminated food

TME Mink Infection from sheep or cattle in food

CWD Mule, deer, elk Unclear

Feline spongiform
encephalopathy Cats Infection from contaminated food

Exotic ungulate
encephalopathy Nyala, oryx, kudu Infection from contaminated food

http://www.emedicine.com/neuro/topic662.htm
OTHER AGENTS OF INFECTION ?

– Is there any infectious agent which

devoid any nucleic acids ?
 PRION ?

Stanley B. Prusiner: PRION from

Proteinaceous infective particle.
..> changed to prion to sound it rhythmic
 The Prion Diseases of Humans

Disease Form of the Diseases

Creutzfeldt-Jacob disease Sporadic, acquired

(CJD) including iatrogenic and Familial

Fatal Familial Insomnia

(FFI)
Familial
Gerstmann-Sträussler-Scheinker disease Familial
GSS)

Acquired
Kuru
 PRION

1. Agent infection.
2. Simpler than viruses.
3. No genome ( No RNA/DNA)
4. Resistant to high temperature.
5. Resistant to proteases.
6. Penetrate “species barrier”
Why ?.
7. Very slow Incubation.
8. Diseases caused: fatal.
9. No anti prion (Yet).
 Comparison of PrPsc and PrPc
PrPsc PrPc
Structure Globular Extended
Protease Yes No
resistance
Presence in Yes No
scrapiefibrils membraneTur
noverDaysHou
rs
Location in or Cytoplasmic vesiclesPlasm
on cells a
Turnover Days Hours
CHARACTERISTIC OF Prion diseases

– Fatal neurodegenerative diseases

– vacuolisation of brain tissue
– deposition of amiloid fibrils
– progressive loss of brain function.
– …> severe dementia and death, NO
treatment available
 Kuru:

• Native of the New Guinea Highlands

• The first human TSE to be recognized
• Incoordination of gait, Strabismus
• Severe of truncal and limb ataxia
• NO fever/convulsion
• died in 3-9 months
• The principal of transmission: Canibalisms.
 Creutzfeldt-Jacob Diseases /CJD :
• Involved: cortex, basal ganglia and spinal cord.
• Incidence: similar throughout the world, except:
Libyan Jews
• Gradual onset of dementia in the middle age/old
• Prodromal: anxiety, fatigue, dizziness, headache
• New variant CJD (- by Prion from BSE)
Animal Prion diseases

– Bovine Spongiform Encephalopathi / BSE.

– Scrapie (sheep/goat).
What is PRION ?:

• ITS ORIGINE ?.

• HOW to propagate ?.
Protein synthesis

• DNA ..>
• Transcription: mRNA (or prec. mRNA)
• Translation: Polypeptide.
• Post-translational Processing: PROTEIN
- signal peptide cleavage
- Acetylation
- Sulfation
- Glycosylation
PROTEIN STRUCTURE:
• Primary structure: peptide bond- aa sequence.
• Secondary structure: motif of Hydrogen bonding,
disulfide bond.
• alpha-helix: Rod-like in structure, stabilize by
H-bonding, C=O and N-H.
• Betha-pleated sheet: H-bonding, C=O and N-H
that far apart.
»parrarel - β sheet
»anti-parrarel -β sheet
• Tertiary structure: three diment. arrangement.