Slow Viruses and Prions

• Slow Infectious disease

– Conventional Viruses
– Unconventional agents (Prions)
• Prions: protein-containing particles with no
detectable nucleic acid that are highly resistant to
inactivation by heat, formaldehyde, and ultraviolet light
• Inactvated by Protein disrupting agents
 Slow Agent Disease In Humans
• Usually involves Central Nervous System
• Long Incubation period
• Gradual Onset
• Progressive,invariably fatal cause
• NO antimicrobial therapy
 Prion Mediated Diseases
• Kuru
• Creutzfeldt Jacob Disease

– Transmissible spongiform encephalopathies

 Transmissibility of Prions
• Kuru,CJD: innoculation from brain of infected
patients to brain of primates followed by serial
transfer to brains of other primates

• ***Kuru,Variant CJD,Mad cow disease: can be

acquired by ingestion
 Ingestion

Survive digestion Amplified within

then penetrate gut dendritic cells in Spleen
mucosa lymphatic tissue

Spread to the Nervous system via sympathetic

nerves
 Other Documented modes of
transmission
• Blood Transfusion
• Iatrogenic
Slow Diseases Caused by
Conventional Viruses
 Progressive Multifocal
Leukoencephalopathy
• Fatal demyelinating Disease of white matter
• Occurs in immunocompromised hosts
• Clinical Picture: visual field defects, mental
status change, weakness
• Rapidly progresses to blindness, coma
• Causative organism: JC virus (Polyoma virus
Papova virus family)
• Non enveloped
• Double stranded DNA genome
• Antibodies found in 75% of normal human
sera
• Disease occurs when latent JC virus is
activated in immunocompromised patients
• DIAGNOSIS: PCR assay of brain biopsy
specimen or spinal fluid
• No effective antiviral treatment
• Cidofovir may be beneficial
 SUBACUTE SCLEROSING
PANENCEPHALITIS(SSPE)
• progressive disease characterized by
inflammatory lesions in many areas of the
brain
• Rare disease of children who were infected
with the measles virus several years earlier
MILD CHANGES IN PERSONALITY

DEMENTIA, DEATH
• Persistent infection by a variant of measles
that cannot complete its replication
 ACQUIRED IMMUNODEFICIENCY
SYNDROME
• Long latent period
• Progressive course
• May involve nervous system
SLOW DISEASES CAUSED BY
PRIONS
• Kuru
• Creutzfeldt Jacob Disease (CJD)
• Variant CJD
• Gerstman Sträussler-Scheinker Syndrome
(GSS)
• Fatal Familial Insomnia
 Kuru
• Progressive tremors and ataxia, not dementia
• ONLY among Fore Tribes in New Guinea
• Caused by ingesting or handling brain tissue
 Creutzfeldt-Jacob Disease
• Found sporadically worldwide
• Affects both sexes
• 1 case per million
• Transmitted iatrogenically
• Main clinical findings:
– Dementia
– Myoclonic jerking
– Ataxia,aphasia,visual loss, hemiparesis
– Terminal stage: mute and akinetic then comatose
• Presumptive diagnosis:
– Spongiform changes in a brain biopsy specimen
– Neuronal loss
– Amyloid plaques
• Specific Diagnosis:Immunohistochemistry
• Serologic tests not useful
• Cannot be grown in culture
• Alternative specimen: Tonsillar tissue
• No treatment
• No vaccine
• 1. Transmissible/infectious
• 2. Hereditary/genetic
• 3. Sporadic
 Gerstman Sträussler-Scheinker
Syndrome
• Cerebellar Ataxia spastic paraparesis
 Fatal familial Insomnia
• Progressive Insomnia, Dysautonomia,
Dementia, Death
 Variant CJD

-occurred in much younger people than usual

and had certain clinical and pathologic findings
different from those found in the typical form of
the disease.
• Native prion protein is homozygous at amino
acid 129
• In individuals who lived or travelled in a
country where bovine spongiform
encephalopathy was detected
• Eg United Kingdom
Slow Diseases in animals
• Scrapie
• Visna
• Bovine Spongiform Encephalopathy
• Chronic Wasting Disease