Unit 4: Virology
212
Lecture 18 – Slow Viruses & Prions
Slow infectious diseases are caused by a heterogenous
group of agents containing both conventional viruses and
unconventional viruses (e.g.,prions).
Prions are protein-containing particles with no decteable
nucleic acid that are highly resistent to inactivation by
heat, formaldehyde, and UV light at doses that will
inactivate viruses.
Prions are inactivated by protein and lipid-disrupting
agents such as phenol, etherr, NaOH and hypochlorite.
The prion protein is encoded by a normal cellular gene
and is thought to function in a signal transduction
pathway in the neurons. The normal prions protein (PRP
c
)
has a significant amount of alpha-helical conformation.
When the alpha-helical conformation changes to a beta-
pleated sheet (PrP
SC
), these abnormal forms aggregate
into filaments, which disrupt neuron function and cause
cell death.
The human prion-mediated diseases are called
transmissible spongiform encephalopathies (TSE). The
term spongiform refers to spongy, Swiss cheese-like holes
seen in the brain parenchyma that are caused by the death
of neurons. The term encephalopathy refers to pathogenic
process in the brain without aigns of inflammation. Prions
can reach the CNS after ingestion by sympathetic nerves
after penetrating the gut mucosa reach the pyre’s patches
then spread to the spleen then to CNS via sympathetic
nerves. It is also possible that the prions reach the CNS
via the blood transfusion and can be transmitted
iatrogenically (via corneal transplant, dura matter grafts,
implanted brain electrodes, and growth hormone extracts
made from human pitutary glands.
Prion caused diseases can be classified into 3
categories:
1) Transmissible (infectious) such as kuru.
2) Hereditary (genetic) such as fatal familial insomnia.
3) Sporadic (neither infectious nor hereditary) such as CJD.
Disease
Pathogenesis
Important features
Kuru
Transmissble
/infectious
Caused by ingestion or
handling brain tissue,
occurred in New Guinea
tribespeople
Creutzfeldt-
Jakob
disease
1- Transmissble
/infectious
Iatrogenic transmission by
corneal transplant, and
growth hormone
2- Hereditary
/genetic
Mutation in germ cells
3- Sporadic
No relationship to any
known cause; possible new
mutation in somatic cells;
most common form
Variant
Creutzfeldt-
Jakob
disease
Transmissble
/infectious
Probably acquired by
eating meat or nervous
tissue from animals with
mad cow disease
Gerstmann
Straussler-
Scheinker
syndrome
Hereditary
/genetic
Mutation in germ cells
Fatal
familial
insomnia
Hereditary
/genetic
Mutation in germ cells
Slow diseases caused by conventional viruses
1) Progressive Multifocal Leukoencephalopathy (PML).
PML is a fatal demyelinating disease of the white matter
and involves multiple areas of the brain. The disease
started with visual field defect, mental status changes, and
weakness and the disease rapidly progress to blindness,
coma and death.
PML is caused by JC virus, a member of polyoma virus
family. It is non-enveloped virus with circular-double
stranded DNA genome. JC infects and kill
oligodendroglia causing demyelination. Neurons are not
affected.
The diagnosis is made typically by PCR assay of the brain
specimen or spinal fluid. There is no antiviral therapy but
cidofovir may be beneficial.
2) Subacute Sclerosing Panencephalitis (SSPE)
SSPE is a slowly progressive disease characterized by
inflammatory lesions in many areas of the brain. It is a
rare disease of children who were infected by measles
virus several years earlier. SSPE is a persistent infection
by a variant of measles virus that cannot complete its
replication.
3) Acquired Immunodeficiency Syndrome (AIDS)