Slow Virus Infection

1. Slow Virus Infection

2. Diseases have a prolonged incubation period • Slow virus diseases may be caused by conventional viruses or unconventional (atypical) agents. • Diseases caused by conventional viruses include; • Progressive multifocal leukoencephalopathy (PML) • Subacute sclerosing panencephalitis (SSPE) and • AIDS dementia complex.

3. Diseases caused by unconventional agents (Prions) In Animals • Scrapie • Transmissible Mink Encephalopathy (TME) • Chronic Wasting Disease of Mule deer (CWD) • Bovine Spongiform Encephalopathy (BSE)

4. In Humans • Creutzfeldt -Jacob Disease (CJD) • Gerstmann-Straussler-Scheinker Syndrome (GSS) • Fatal Familial Insomnia (FFI) • kuru

5. Characteristics of prion disease • They are confined to the CNS. • They have a prolonged incubation period. • They show a slow progressive fatal course. • They show a spongiform encephalopathy. • They result in vacuolation of neurons.

6. Subacute Spongiform Encephalopathies are also recognized as the transmissible cerebral amyloidoses (TCA) • Prions are unconventional filterable agents with unusual physical, chemical and biological properties. • Lack detectable nucleic acids and consist of aggregates of a protease-resistant, hydrophobic glycoprotein with a molecular weight of 27-30 kd.

7. Pathogenesis • Vacuolation of neurons and formation of amyloid- containing plaques and fibrils. • Proliferation and hypertrophy of astrocytes and fusion of neurons and adjacent glial cells. • Prions reach high concentrations in the brain and can be isolated from tissues other than the brain but only the brain shows any pathology. • No inflammation or immune response is generated to the agent.

8. gliosis of cerebral cortex spongiform degeneration in the cerebral cortex from patient with CJD (H and E) PrP deposits in cerebellum from patient with G-S-S disease (immunostain)

9. Localization of Different Prion Diseases • In fatal familial insomnia (FFI), mutated prions accumulate in the thalamus, with the result that the patients are unable to sleep. • In Creutzfeldt-Jakob disease, the prion protein accumulates primarily in the cerebral cortex. • In kuru and GSS, PrPSc accumulates in cerebellum. • In BSE, PrPSc accumulates in brain stem.

10. Thalamus Cortex CJD FFI Different shapes of the prion protein accumulates in different regions of the brain

11. Clinical Syndromes • The incubation period for CJD and Kuru may be as long as 30 years. Once symptoms become evident the patient dies within a year. • They were first defined as Creutzfeldt-Jakob disease named after the German neurologists, who each described a few cases.

12. Fatal Familial insomnia (FFI) • FFI is a disease of man that results in progressive untreatable insomnia, loss of circadian rhythm, endocrine disorders, motor disorders, and dementia. • It seems that the hypothalamus function is the target.

13. Kuru • Characterized by cerebellar ataxia and a shivering-like tremor. • Progresses to complete motor incapacity with dysarthria and total loss of speech and then to death in less than 1 year from onset. • The disease has three phases, ambulant, sedentary, and terminal. • Emotional liability leading to outbursts of pathologic laughter is frequent; sometimes appearing in the first stage of the disease

14. Smiling and laughter are terminated slowly (laughing death, a journalistic synonym). Nearly true euphoria may be observed. • Some, rarely develop pathologic belligerence to all disturbances by family members. • Terminally, patients develop incontinence, dysphagia with thirst and starvation, flaccidity, inanition, mutism and unresponsiveness.