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CHAPTER 20
Persistent Viral Infections of the Central Nervous
System
Persistent viral infections are those in which termination of early symptoms and disease
is not accompanied by elimination of the virus from the host but persistence of viral
genetic material in the host. While the molecular mechanisms of persistent viral
infections are not clearly understood, three broad conditions must be satisfied for a virus
to establish a persistent infection in a host. These conditions are: (1) Infection of the host
cell by the virus should not be cytolytic. (2) Viral genome must be maintained by various
mechanisms. (3) Virus has to avoid detection and elimination by the host’s immune
system
I. General Features
1. Viral persistence occurs after asymptomatic infection or termination of early
symptoms or disease
2. Viruses that persist are less cytolytic or cytopathic to the cells in which they
persist
3. Viral DNA genomes either integrate or persist as extrachromosomal episomes
4. Mechanisms of persistence of RNA genomes in infected cells not understood
5. Viruses avoid detection and elimination by the host’s immune system
6. Viruses infect immune privileged sites such as CNS to cause persistent infection
7. Progressive neurologic diseases
8. Include conventional viruses and unconventional agents
9. “Prions” do not produce immune or inflammatory responses
10. Persistence can be due to a variety of mechanisms
II. DISEASES ASSOCIATED WITH CONVENTIONAL
AGENTS
A. Subacute Sclerosing Panencephalitis
1. Persistence of measles virus after acute childhood infection
B. Progressive Postrubella Panencephalitis
1. Can be a late sequela of congenital rubella infection
2. Rubella virus has been isolated from brain tissue
C. Progressive Multifocal Leukoencephalopathy
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1. Progressive neurologic disease of severely immunocompromised persons
2. Due to a polyomavirus (JC virus)
D. Persistent Enterovirus Infection
1. Chronic CNS infection due to an echovirus or other enterovirus
2. Associated with humoral immunodeficiencies
3. Temporary improvement with hyperimmune globulin
E. AIDS Dementia Complex
1. Persistent infection of the CNS in many patients with symptomatic AIDS
2. Late stages of AIDS
III. HUMAN DISEASES CAUSED BY UNCONVENTIONAL
AGENTS: SUBACUTE SPONGIFORM
ENCEPHALOPATHIES
I. Prions
1. Prions cause bovine spongiform encephalopathy in cattle, scrapie in sheep, and
five fatal CNS diseases in humans
2. Diseases are known as “spongiform” encephalopathies because of the vacuolar
changes in the cortex and cerebellum
3. Incubation periods are months to years and courses are protracted and
inevitably fatal.
4. A prion is a small proteinaceous infectious particle that lacks nucleic acids
5. A prion is converted from a normal form (NP) into a disease-causing form by a
change in conformation to a protein designated PP
5. PP is encoded by a normal cellular gene
6. PP is the prion that is responsible for transmission and infection
7. The conformational change is also the way that prions multiply
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8. During scrapie infection, prion protein may aggregate into amyloid-like
birefringent rods and filamentous structures termed scrapie-associated fibrils
II. Kuru
1. Kuru was a subacute, progressive neurologic disease with ataxia, hyperreflexia,
and spasticity leading to progressive dementia, starvation, and death
2. Clinical disease develops 4 to 20 years after exposure.
3. Women and children of the Fore people of New Guinea
4. Transmissible to primates
5. Associated with cannibalism
6. Since the elimination of cannibalism from the Fore culture, kuru has disappeared.
III. Creutzfeldt–Jakob Disease
1. Forgetfulness and disorientation progress to overt dementia and the
development of changes in gait, increased tone in the limbs, involuntary
movement, and seizures
2. Progressive disease, usually occurring among elderly
3. Found worldwide, with an incidence of disease of one case per million per year
4. Natural mode of acquisition is unknown
5. Infection has also been transmitted by dura mater grafts, corneal transplants, by
contact with contaminated electrodes or instruments used in neurosurgical
procedures, and by pituitary-derived human growth hormone
6. Incubation period of the disease is 3 to greater than 20 years
7. Transmitted to chimpanzees, mice, and guinea pigs by inoculation of infected
brain tissue, leukocytes, and certain organs
8. Pathology identical to kuru
9. Scrapie-like structures seen in brain
10. No effective therapy for Creutzfeldt–Jakob disease. All cases have been fatal.
A. PREVENTION
1. Nosocomial infections preventable by avoidance of potentially infectious
materials, careful sterilization
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IV. Bovine Spongiform Encephalopathy (“Mad Cow Disease”)
and “Variant Creutzfeldt–Jakob Disease”
1. Identified in 1986, after it began striking cows in the United Kingdom
2. Source traced to a food supplement that included meat and bone meal from
dead sheep.
3. The incubation period in cattle was determined to be 2 to 8 years
4. Prion that causes BSE survived the heat of cooking and was transmitted to
5. It appears that destruction of diseased cattle and the changes in livestock feeds
have prevented further cases.
V. Gerstmann-Straüssler-Scheinker Disease
1. Gerstmann-Straüssler-Scheinker disease similar to Creutzfeldt–Jakob disease
but evolves more slowly
2. The familial nature of this disease raises the question of vertical transmission
versus inherited susceptibility
VI. Fatal Familial Insomnia
1. Familial prion disease in which a syndrome of sleeping difficulty is followed
by progressive dementia
2. Occurs in patients aged 35 to 61, culminating in death within 13 to 25 months
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