Slow Viruses and Unconventional Agents

Question 1

Slow Viruses

General Info

Answer 1

a. They have a long incubation period (usually years)
b. They follow a slow but relentless course leading to death
c. They tend to have a genetic predisposition
d. They often re-emerge from latency during immune suppression

Question 2

Slow Diseases caused by Conventional viruses

Answer 2

a) AIDS
b) Progressive Multifocal Leukoencephalopathy (PML)
c) BK Nephropathy
d) Subacute Sclerosing Panencephalitis (SSPE)

Question 3

AIDS

Answer 3

It’s caused by the Lentivirus Human immunodeficiency virus (HIV).
HIV has a long incubation period

Question 4

Multifocal Leukoencephalopathy (PML)

Answer 4

JC virus (papovavirus family) causes Progressive
Multifocal Leukoencephalopathy (PML).
PML is only seen in immunocompromised individuals.
PML is a progressive demyelinating disease of
the brain (JC virus infects oligodendroglia). There is
no inflammation in PML.
PML originates via the “reactivation” of JC virus infection in the immunocompromised (some cases have been reported in patients undergoing immune treatment for multiple sclerosis).
PML progresses quickly to blindness, dementia,
coma, and patients die within 6 months

Question 5

BK nephropathy

Answer 5

BK nephropathy is caused by a papovavirus.

Occurs in up to 10% of renal transplants and results in high rate of transplant failure.

Question 6

Subacute Sclerosing Panencephalitis (SSPE)

Answer 6

SSPE is a rare disease seen in school-age
children.
SSPE has an insidious onset of intellectual
deterioration, psychological disturbances with slow decline interrupted by remissions. It is generally fatal with terminal paralysis and blindness.
SSPE has a long incubation period

Question 7

SSPE and Measles

Answer 7

SSPE is associated with helical nucleocapsids and abnormally high antibodies to measles together with measles viral antigens.
SSPE patients all had uncomplicated of measles 4-17 years earlier typically at an early age (2 or younger)
Measles virus can be isolated from SSPE brains though how it causes the disease is not known.
The incidence in those who had the measles virus is lower than those with natrually occuring measles.

Question 8

Prions

Answer 8

Prions are hypothesized to be infectious proteins.
Prions are protein-containing particles that lack any detectable nucleic acid and are highly resistant to proteolytic enzymes.

Question 9

Characteristics of Prions

Answer 9

a. have a long incubation period (usually years)
b. follow a slow but relentless course leading to death
c. cause diseases that are confined to the CNS
d. produce a spongiform encephalopathy
e. may have a genetic predisposition

Question 10

SCRAPIE (a prion disease of sheep)

Answer 10

1. Scrapie is a chronic progressive CNS (especially cerebellum) disorder of adult sheep.
2. This is no pathological evidence of an infectious process.
3. The genetic background of the sheep is important. Certain inbred lines are much more susceptible.

Question 11

Human Diseases caused by Prions

Answer 11

Human prion-mediated diseases are called transmissible spongiform encephalopathies. The five known human transmissible spongiform encephalopathies caused by prions are:

1) KURU
2) Creutzfeld-Jacob disease (CDJ),
3) Variant CDJ,
4) Gerstmann-Straussler-Scheinker syndrome (GSS)
5) Fatal familial insomnia.

Question 12

Kuru

Answer 12

1. Kuru is a progressive degenerative disorder of the CNS, especially the cerebellum.
2. It is limited to a small stone-age tribe in New Guinea [Fore people].
3. At its peak, it caused 1/2 of the total mortality in this tribe.
4. No obvious environmental factor involved. It was once considered purely a genetic defect. Parallels to scrapie were noted.
5. Kuru symptoms and neuropathology, SPONGIFORM ENCEPHALOPATHY,
   were reproduced in chimps by intracerebral
   injection of brain material from human cases. Ingestion of infected brains also transmits the disease.
6. The properties of the infectious agent resemble those of scrapie.
   7.The incidence is now low because of reduced cannibalism.

Question 13

Creutzfeld-Jacob Disease

Answer 13

1. The most common human spongiform encephalopathy is CREUTZFELD-JACOB DISEASE. Like Kuru, Creutzfeld- Jacob disease has been transmitted to primates. Some cases of Creutzfeld-Jacob disease are the result of an inherited mutation but most are spontaneous, with no established cause. Some IATROGENIC (inadvertently caused by physicians) (iCJD) cases have been traced to corneal transplants from a donor with undiagnosed disease and to other medical procedures (including contaminated surgical instruments and previously to growth hormone prepared from pituitary glands of undiagnosed Creutzfeld-Jacob patients).
2. Some CJD disease is linked to familial genetics and an increased risk of CJD (fCJD).
3. Some CJD is sporadic (sCJD)

Question 14

VARIANT CDJ (vCJD)

Answer 14

1. A spongiform encephalopathy of cows (“mad cow disease”) reached epidemic status in Great Britain as a result of using brains and bone marrow from cows and sheep in the manufacture of bovine food.
2. An outbreak of “atypical human Creuzfeld-Jacob disease” (vCJD) in Great Britain has been linked epidemiologically to eating beef from infected cows.