IV. Kuru: Pathogenesis and Characterization of Virus

Clarence J. Gibbs Jr.National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20014

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D. Carleton GajdusekNational Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20014

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Kuru, a subacute, progressive degenerative disease of the central nervous system of man, has an infectious etiology and is experimentally transmissible to other primates. Thus far, 91 chimpanzees have been inoculated with specimens from 37 human kuru victims (44 animals) or from other chimpanzees and spider monkeys with experimental kuru (47 animals). Among these, the disease has already developed in 35 chimpanzees: in 15 on primary passage, in 10 on second passage, in eight on third passage, and in two on fourth passage. Brain tissue from 11 human victims has induced disease in 15 animals, after incubation periods ranging from 14 to 38 months. The kuru virus remains viable in human brain tissue stored at -70°C for more than 5 years. The virus is serially transmissible in chimpanzees by intracerebral and peripheral routes of inoculation and can be recovered from visceral tissues as well as brain tissues. Serial passage is associated with a reduced incubation period, and the virus is detectable in the brains of chimpanzees before the onset of clinical disease. The virus has also been transmitted from a chimpanzee to spider monkeys after an incubation period of 2 years. In suspensions of both human and chimpanzee brain tissue the virus passes through a 220 µm millipore filter. By the intracerebral route chimpanzee brain tissue has an infectivity titer equal to or greater than 10-7.5 per ml. The virus is not completely inactivated after exposure to a temperature of 85°C for 30 minutes, and it remains viable after lyophylization and storage at a temperature of -20°C. Virus infectiousness for chimpanzees by the intracerebral route of inoculation was not neutralized at a dilution of 10-3 when mixed with pooled, undiluted serum from human kuru victims or pooled, undiluted serum from neighboring normal Anga (Kukukuku) people of the Eastern Highlands of New Guinea. Experiments are under way to investigate the possibility of infection after oral inoculation of chimpanzees with human and chimpanzee kuru-infected tissues.

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