Page 383 - Review of Medical Microbiology and Immunology ( PDFDrive )

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Slow Viruses & Prions

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CHAPTER C ONTENT S

Introduction
Slow Diseases Caused By Conventional Viruses
Scrapie
Progressive Multifocal Leukoencephalopathy
Visna
Bovine Spongiform Encephalopathy
Subacute Sclerosing Panencephalitis
Acquired Immunodeficiency Syndrome
Chronic Wasting Disease
Slow Diseases Caused by Prions
Kuru
Summaries of Organisms
Creutzfeldt-Jakob Disease Self-Assessment Questions
Practice Questions: USMLE & Course Examinations
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Variant Creutzfeldt-Jakob Disease (vCJD)

INTRODUCTION
conformational change. Prions are described in more detail
in Chapter 28.
“Slow” infectious diseases are caused by a heterogeneous
Pathogenic prion proteins can be thought of conceptu-
group of agents containing both conventional viruses and
ally as misfolded proteins. These misfolded proteins not
unconventional agents that are not viruses (e.g., prions).
only cause CJD in humans and “mad cow” disease in cattle
Prions are protein-containing particles with no detect-
able nucleic acid that are highly resistant to inactivation by
other important diseases of the central nervous system,
heat, formaldehyde, and ultraviolet light at doses that will
inactivate viruses. Note that prions are resistant to the tem- but are suspected of being involved in the pathogenesis of
In humans, the “slow” agents cause central nervous
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peratures usually employed in cooking, a fact that may be
system diseases characterized by a long incubation period,
important in their suspected ability to be transmitted by
a gradual onset, and a progressive, invariably fatal course.
food (see variant Creutzfeldt-Jakob disease [CJD] later).
There is no antimicrobial therapy for these diseases. Note
Prions are, however, inactivated by protein- and lipid-dis-
rupting agents such as phenol, ether, NaOH, and hypochlo-
replication of those viruses that cause these slow diseases.
rite (see Chapter 28).
The replication rate of these viruses is similar to that of
The prion protein is encoded by a normal cellular gene
most other viruses.
and is thought to function in a signal transduction pathway
The human prion-mediated diseases (e.g., kuru and
C
in neurons. The normal prion protein (known as PrP , or
CJD) are called transmissible spongiform encephalopa-
prion protein cellular) has a significant amount of alpha-
helical conformation. When the alpha-helical conforma-
cheese–like holes seen in the brain parenchyma that are
SC
tion changes to a beta-pleated sheet (known as PrP , or
caused by the death of the neurons (Figure 44–1). No virus
prion protein scrapie), these abnormal forms aggregate into thies (TSE). The term spongiform refers to the spongy, Swiss
particles are seen in the brain of people with these diseases.
filaments, which disrupt neuron function and cause cell
The term encephalopathy refers to a pathologic process
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death. Prions, therefore, “reproduce” by the abnormal beta-
in the brain without signs of inflammation. In contrast,
pleated sheet form recruiting normal alpha-helical forms to
encephalitis refers to an inflammatory brain process in
change their conformation. Note that the normal alpha-
TSEs, there are no inflammatory changes in the brain.
helical form and the abnormal beta-pleated sheet form
have the same amino acid sequence. It is only their confor-
The transmissibility of the agent of kuru and CJD
(“prions”) was initially established by inoculation of
mation that differs. A specific cellular RNA enhances this
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