Unconventional viruses and the origin and disappearance of kuru.

Kuru was the first chronic degenerative disease of man shown to be a slow virus infection, with incubation periods measured in years and with a progressive accumulative pathology always leading to death. This established that virus infections of man could, after long delay, produce chronic degenerative disease and disease with apparent heredofamilial patterns of occurrence, and with none of the inflammatory responses regularly associated with viral infections. Soon thereafter, several other progressive degenerative diseases of the brain were likewise attributed to slow virus infections (see Tables 1 and 2). These include delayed and slow measles encephalitis, now usually called subacute sclerosing panencephalitis (SSPE), progressive multifocal leukoencephalopathy (PML), and transmissible virus dementias usually of the Creutzfeldt-Jakob disease (CJD) type. Thus, slow virus infections, first recognized in animals, became recognized as a real problem in human medicine. Kuru has led us, however, to a more exciting frontier in microbiology than only the demonstration of a new mechanism of pathogenesis of infectious disease, namely the recognition of a new group of viruses possessing unconventional physical and chemical properties and biological behavior far different from those of any other group of microorganisms. However, these viruses still demonstrate sufficiently classical behavior of other infectious microbial agents for us to retain, perhaps with misgivings, the title of “viruses”. It is about these unconventional viruses that I would further elaborate. The group consists of viruses causing four known natural diseases: two of man, kuru and CJD, and two of animals, scrapie in sheep and goats, and transmissible mink encephalopathy (TME) (Table 1). The remarkable unconventional properties of these viruses are summarized in Tables 3 and 4. Because only primate hosts have been available as indicators for the viruses