Slow viruses

Prions are responsible for the so-ealled slow virus diseases, a distinet group of unusual neurologieal disorders. They are believed to be markedly resistant to inactivation by many ehemieal and physical agents but because they have not been purified, it is at present diffieult to state whether this is an intrinsic property of prions or whether it results fkm the proteetive effect of host tissue present. Certainly very high coneentrations of a bioeide aeting for long periods may be necessary to produee inactivation. 

The prion diseases are a closely related group of neuro-degenerative conditions which affect both humans and animals. They have previously been described as the subacute spongiform encephalopathies, slow virus diseases and transmissible dementias, and include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and the human prion diseases, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and kuru. Prion diseases are... 

The Producing System. The questions of particular concern here are the nature of the system used to manufacture the desired substance, and the precision with which it is controlled. If the system consists of prokaryotic cells, then how well-defined is their provenance and how is their consistency demonstrated If mammalian cells are employed, their lineage must be considered. In both instances, it is important to ensure that extraneous virus, infections, DNA and less well-defined factors such as slow viruses are excluded by the origins and history of the producer strain, or because the physical (e.g., filtration) or chemical (pH, solvents, affinity separation) nature of the production process can be relied upon to exclude passage of an infectious agent. 

Baculovirus Improved procedure Infection of insect cells High expression yields Relatively slow virus production Different post-translational processing... 

The cause of AD is unknown although many hypotheses abound. The gene for one of the excessive amyloid proteins(b-type) has been associated with chromosome 21 at a point not far from a locus linked to some cases of familial Alzheimer s. Victims of Down s syndrome have an extra copy of chromosome 21 and usually fall prey to AD in their 4O s should they live to that age. However no all AD victims have a 21 mutation. Other causative theories involve accumulations of aluminum in the brain or the presence of a slow virus or an infectious protein substance called a prion. 

HIV-1 is a member of the group of slow viruses or lentiviruses.730 Other lentiviruses include the human HIV-2,731 an immunodeficiency virus that attacks cats causing leukemia,732 and the human leukemia virus... 

Slow viruses are becoming increasingly suspect in the instances of much more common diseases, particularly the autoimmune diseases. An autoimmune disease may be defined as a disease wheiein the immune system of the body does not direct its attack on an invading foreign substance, but instead at the body s own tissue. Many authorities consider rheumatoid arthritis and multiple sclerosis as autoimmune diseases. The precise causes of these diseases have remained obscure. Multiple sclerosis is a demyelinating disease and has variously been described as an autoimmune disease, a viral disease, or an autoimmune disease provoked by a virus. Epidemiological studies indicate that from 3 to 23 years may elapse between the time of exposure to the virus and the onset of symptoms. Further evidence points to involvement of a myxovirus. Measles virus is of this kind. 

Certain scrapie-like diseases of sheep in Iceland and some chronic encephalopathies in man (including kuru, the laughing disease of New Guinea) are the result of slow virus infections with long incubation periods. 1-Methylisatin 3-thiosemicar-bazone has been found to reduce the reverse transcriptase activity and cytopathic effect of the RNA slow viruses producing the sheep diseases and hence may provide a chemotherapeutic method for their control118. ... 

Finally, there is an increasing need to evaluate the importance of environmental toxins in the pathology of Alzheimer s disease. There has been much interest lately in the role of aluminium as a causative factor, while the studies of dementia associated with the acquired immunodeficiency syndrome have focused attention on the effects of slow viruses in causing brain cell death. 

Infectious disorders Chronic meningitis Tuberculosis, fungal, parasitic HIV disease Tertiary syphilis Slow virus (Creutzfeldt-Jakob disease) Treatment of infection... 

Draganescu N, Antipa C, Girjabu E, Melencu M. Endemic Balkan nephropathy, a slow virus disease Rev. Roum. Med.-Virol. 1983 ... 

New working hypotheses should take into account slow viruses as precipitating agents that are tropic for B-cells, acting close to the time of diagnosis (Bottazzo et al., 1985). 

Dickinson AG (1976) Scrapie in sheep and goats. In Kimberlin RH (ed) Slow virus diseases of animals and man. North-Holland Publishing, Amsterdam, pp 209-241... 

Prions are now thought to be what were formerly called slow viruses, because the resulting diseases took months or years or decades to develop (Voet and Voet, 1995, p. 1116). These particular diseases pertain to the mammalian nervous systan. None of the diseases exhibit inflammation or fever, indicating that the immune system is neither activated nor impaired by the disease. As has been indicated, the word prion stands for proteinaceous infectious particle, and the protein itself is called PrP, for prion protein. 

Unspecified viral particles [30], an unidentified cy-topathogenic agent, serially propagated slow viruses [31], and an unknown virus associated with foci of... 

Many other possible causes of dialysis dementia have been proposed. These inclnde other trace element contaminants, normal pressure hydrocephalus, slow virus infection of the central nervous system, and regional alterations in cerebral blood flow (Arieff, 1990). Slow virus infection of the nervous system is a possible etiology for dialysis dementia. The clinical manifestations resemble those of other slow virus infections, such as Kuru or Creutzfeldt-Jakob disease (Selkoe, 1978 4714 Gajdusek, 1985 1662). 

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