Nina Ian John “G” Rachel Mark Jocelle Edo Gienah Jho Kath Aynz Je Glad Nickay Ricobear

Teacher Dadang Niňa Arlene Vivs Paulfie Rico Ren Mai Revs Mavis Jepay Yana Mayi Serge Hung Tope Ag Bien

S3 L15: Slow Viruses and Prions by Dr. Antonio Camacho November 26, 2010

SLOW VIRUS INFECTIONS o Ethanol

o Glutaraldehyde
General Characteristics: o UV and ionizing radiation
o Non-ionic detergents
Prolonged incubation period (months or years) Inactivated by:
Protracted, progressive clinical course o Autoclaving (121°C for 1 hour)
Refers to the TEMPO of the disease and NOT the growth rate of o 5% sodium hypochlorite
the virus o Sodium hydroxide
Conventional viruses o Proteases, urea, other protein denaturants
Unconventional viruses (AKA unconventional agents or atypical
viruses/agents) Prions

Conventional Viruses Protein is present in purified preparations of infectious material

Progressive multifocal leukoencephalopathy (PML)
Subacute sclerosing panencephalitis (SSPE)
Progressive rubella panencephalitis (PRP)
HIV
Rabies
Progressive Multifocal Leukoencepalopathy
Rare, progressive, fatal demyelinating disease of the CNS
Symptoms: memory loss, loss of coordination, mentation problems,
vision problems
Caused by certain members of the polyomavirus family  JC virus
Frequently have some abnormality in the immune system (develops
in up to 5% of patients with AIDS)
Probably due to a reactivation of a viral infection
Subacute Sclerosing Panencephalitis (SSPE)
Rare complication of measles infection
Develops ~ 1 – 10 years after initial infection
Progressive fatal disease
Symptoms: mental and motor deterioration
Risk factor: acquiring primary measles at an early age
Associated with defective forms of the virus in the brain
Difficult to isolate infectious virus from patients
Treatments which destroy protein, destroy infectivity, but, treatments
which destroy nucleic acid do NOT destroy infectivity
PrP (prion protein)
Causes diseases which are confined to the CNS
Have a prolonged incubation period
Show a slow, progressive, fatal course of disease
Show a spongiform encephalopathy (transmissible spongiform
encephalopathies)
Characteristically results in vacuolation of neurons
Can cause formation of fibrillar aggregates, which contain PrP and
have amyloid-like characteristics
Prion Protein (PrP)
Stanley B. Prusiner – 1997 Nobel Prize in Physiology and Medicine
Preparations of highly purified infectious material contain large
amounts of PrP
Encoded by a host cellular gene – short arm of chromosome 20
30-kD normal cellular protein in neurons
Normal form – α-helix
PrPres (resistant to protease)
PrPsc (first found in scrapie infections)
o Diseased form
o “amyloid plaques”
o β-pleated sheet

Progressive Rubella Panencephalitis (PRP)

Very rare consequence of rubella virus infection

Symptoms: mental and motor deterioration
Initial infection is usually congenital or soon after birth
Onset of PRP 8-19 years old

Unconventional Viruses or Agents: Prions

Similar to viruses
o Small
o Filterable
o Needs host cells Why is the protein infectious?
o No machinery for energy generation or protein synthesis Hypothesis:
Different from viruses The resistant form can convert the normal form to the resistant form,
o No detectable virions in infected tissues which will then be
o No detectable virions in purified preparations of infected able to convert more normal to resistant itself, and thus, the rate of
material conversion will gradually amplify as the concentration of resistant
o No nucleic acid; if present, very small form increases.
o Very resistant
Resistant to or partially inactivated by:
o Formaldehyde

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 Prion Protein (PrP)
Immune response
o Do not cause an inflammatory response
o Do not induce interferon
o No antibody response

Transmissible Spongiform Encephalopathies (TSEs)

AKA transmissible cerebral amyloidosis, prion diseases

Rare
Acquired, inherited, or occur sporadically
Human
o Kuru
o Creutzfeldt-Jakob disease (CJD)
o Gerstmann-Straussler-Scheinker (GSS) syndrome
o Fatal familial insomnia (FFI)
o New variant CJD (“human BSE”)
Animal
o Scrapie (sheep and goats)
o Transmissible mink encephalopathy
o Bovine spongiform encephalopathy (BSE)
Diagnosis
o Probable
 Clinical picture
 EEG
o Final
 Postmortem examination of the brain
 vCJD
 PrPsc in peripheral lymphoid tissue (tonsil
biopsies)
Why are there differences in prion diseases?  Western blot assay

Creutzfeldt-Jakob Disease (CJD)

1-3 cases per million population per annum

16 - 80+ years; usually, 50 - 70 years of age
Route of transmission – not known
No evidence for direct person-to-person transmission
Transmissible to animals
Sporadic – most cases
Familial
o 10%
o autosomal dominant
o Libyan-born Jews in Israel and in a rural area in
Czechoslovakia
Iatrogenic (medical manipulations)
o Cornea transplants
o Dura mater transplants
o Use of improperly sterilized equipment (e.g.,
intracerebral electrodes) in neurosurgery
o Human cadaver growth hormone administration
Dementia
o most common - rapidly progressive
Prodrome
o vague personality changes
Alterations in higher cortical function, ataxic gait, visual disturbance,
involuntary movement, dysphagia/dysarthria
Mental deterioration vegetative state
Entire clinical course typically lasts approx. 4 months before death
occurs; others 2 years
Clinical triad (up to 75% of cases):
o mental deterioration
o myoclonus
o periodic sharp EEG complex
Pathology
o Limited to the CNS
o Atrophy generally less severe than AD
o Three major histologic changes:

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  spongiform changes – gray matter; diffuse or
focal Kuru
 gliosis Confined to the Fore people in the Eastern Highlands of Papua New
 neuronal loss Guinea
Transmitted by rites for the dead – autopsy and ritual cannibalism
Gerstmann-Straussler-Scheinker (GSS) syndrome Prominent cerebellar signs (ataxia and tremors) and dementia with
eventual death
Kuru-like symptoms No evidence for transmission to fetus, via milk or intimate sexual
Familial contact
o Most cases Pathology
o Autosomal dominant o Cerebral gray structures
o Genetically transmitted subclass of CJD  spongiform changes
o Almost exclusively in the northern hemisphere, including o Cerebellum
western Europe, Japan, and the US; likely worldwide  amyloid plaques (“kuru plaques”)
Transmissible to animal  large single amyloid core surrounded by a
fine, fibrillar, rim-like halo
Fatal Familial Insomnia (FFI)

Progressive untreatable insomnia ----------------------------------------END OF TRANS-----------------------------------------

Loss of circadian rhythm
Endocrine disorders, motor disorders, dementia
Familial
Transmissible to animals
Hypothalamus

New variant CJD (nvCJD, vCJD)

“Human BSE”?
o Strong association with exposure to BSE-contaminated
beef
Younger – under 40 years of age
Psychiatric problems more prominent
More protracted disease
1996
128 in UK
6 in France
1 each in Ireland, Italy and in the US
Pathology
o Distinctive neuropathological appearance
o More PrP amyloid plaque-type deposits than in typical
CJD cases
o More infectious agents in the peripheral tissues, esp. in
the lymphoreticular tissues Ang trans na ito ay inihahandog ng:

MICROBIOMAN (+ 1 )

From 1st row (L to R): Paulfie, Edo, Teacher

From 2nd row (L to R): Niña, Nickie, Turay

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