Slow viral diseases of the central nervous system

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Slow viral diseases of the central nervous system

• tempo of clinical disease
• protracted incubation period
• protracted course of disease

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SLOW INFECTIONS IN HUMANS

• TYPICAL AGENTS
• SV40-like viruses (PML)
• measles virus (SSPE)
• rubella virus (PRP)
• ATYPICAL AGENTS
• Kuru,
• Creutzfeld-Jakob disease (CJD)
• new variant CJD disease (nvCJD, vCJD)

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Progressive multifocal leukoencephalopathy

• papovaviruses, polyoma group, SV40-like (JC virus
  etc)
• progressive, usually fatal
• HAART may help in AIDS patients
• non inflammatory
• demyelination (oligodendrocytes)

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SYMPTOMS

• weakness
• speech problems
• cognitive problems
• headaches
• gait problems
• visual problems
• sensory loss
• seizures

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Progressive multifocal leukoencephalopathy

• 70-80 population are seropositive
• associated with immunosuppression
• 1979 1.5/10,000,000
• 1981-1990 7.2/1,000 AIDS patients
• 2000 up to 5 AIDS patients

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MEASLES VIRUS

• paramyxovirus family (morbillivirus genus)
• sub-acute sclerosing panencephalitis
• inflammatory disease
• defective virus
• early infection with measles is a risk factor
• rare

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RUBELLA VIRUS

• togavirus family (rubrivirus genus)
• progressive rubella panencephalitis
• inflammatory disease
• defective virus
• congenital / very early infections
• very very rare

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transmissible subacute spongiform encephalopathies
transmissible cerebral amyloidoses

• prion diseases

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transmissible spongiform encephalopathies (TSEs)

• human
• Kuru
• Creutzfeldt-Jakob disease (CJD)
• Gerstmann-Straussler-Scheinker syndrome
• Fatal familial insomnia (FFI)
• new variant CJD (human BSE?)
• animal
• scrapie (sheep and goats)
• transmissible mink encephalopathy
• bovine spongiform encephalopathy (BSE)
• etc

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ATYPICAL AGENTS

• atypical viruses
• atypical agents
• prions

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ATYPICAL AGENTS

• SIMILAR TO VIRUSES
• small
• filterable
• need host cells
• no machinery for energy generation of protein
  synthesis

• DIFFERENT FROM VIRUSES
• no detectable virions in infected tissues
• no detectable virions in purified infectious
  material
• if nucleic acid is present, very small
• very resistant

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• RESISTANT TO OR ONLY PARTIALLY INACTIVATED BY
• formaldehyde
• ethanol
• glutaraldehyde
• ultraviolet and ionizing irradiation
• non-ionic detergents
• INACTIVATED BY
• autoclaving (121C for one hour) (gt standard)
• 5 sodium hypochlorite
• sodium hydroxide
• proteases, urea, other protein denaturants

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purified infectious material

• protein present
• proteases inactivate
• nucleic acid controversial

PRION
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PRION DISEASE

• CNS
• LONG INCUBATION
• SLOW COURSE OF DISEASE
• SPONGIFORM ENCEPHALOPATHY
• VACUOLATION OF NEURONS
• RARE IN MAN

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SCRAPIE

• sheep
• loss of muscular control
• wasting
• glial proliferation
• vacuolation of neurons
• amyloid plaques
• abnormal properties infectious material

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KURU

• tremors, ataxia, weakness
• dementia, death
• amyloid plaques
• spongiform changes

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CREUTZFELDT-JAKOB DISEASE

• appearance of brain at autopsy
• dementia, myoclonus, ataxia
• 16-80, usually 50-70
• 10 familial
• also sporadic

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CREUTZFELDT-JAKOB DISEASE

• no evidence for direct person to person
  transmission
• blood
• milk
• other body fluids
• intimate social contact

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CREUTZFELDT-JAKOB DISEASE

• iatrogenic CJD
• human cadaver growth hormone
• human cadaver gonadotropin
• dural mater grafts
• corneal transplantation
• neurosurgical instruments
• stereotactic EEG electrodes

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The Times (London)
Dura mater - used in brain surgery
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OTHER HUMAN PRION DISEASES

• Gerstmann-Sträussler-Scheinker syndrome (GSS)
  (familial)
• motor
• new variant CJD (nvCJD, vCJD)
• psychiatric
• fatal familial insomnia (FFI)
• circadian rhythm problems

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IMMUNE RESPONSE

• no inflammatory response
• no interferon induction
• no anti-body response
• no cell-mediated response

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Walt Kelly
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RES
PrP
PrP
SC
PrP
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INHERITED FORMS
RES
PrP
PrP
SC
PrP
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WHY ARE THERE DIFFERENT FORMS OF THE DISEASE?
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PLAQUES

• PrP
• NOT THE SAME AS IN ALZHEIMERS

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THE END