PRIONS and slow viruses

[liveonearth]

--"slow" infectious diseases are caused by viruses and by prions
--prions are protein-containing particles with no detectable nucleic acid that are highly resistant to heat, formaldehyde and UV light at doses that would kill viruses
--prion protein is encoded by a normal cellular gene and may fx in neuronal signal transduction
--prion undergoes conformational change and aggregates into filaments that disrupt neuron fx and cause cell death
--prion "reproduction" is the formation of the abnormal beta-pleated sheet from normal alpha helices
--"slow" dz = long incubation, gradual onset, progressive and fatal course
--human dz incl: kuru and CJD (TSE = transmissible spongiform encephalopathies -->swiss cheese brain)
--encephalopathy = brain pathology without inflammation
--encephalitis = inflam
--three categories of prion-caused disease: transmissible (infectious, ex: kuru), genetic/hereditary (fatal familial insomnia) and sporadic (neither infectious nor genetic), could be due to spontaneous mutation
--PML = progressive multifocal leukoencephalopathy = fatal demyelinating dz, usu w/ visual field defects, mental status changes, weakness, progresses to blindness, dementia, coma, death in 6 mo, can be caused by monoclonal antibody natalizumab used for treating MS
--SSPE = subacute sclerosing panencephalitis = slow inflam lesions in brain, rare in children years after measles, begins with personality change progresses to dementia and death.
--SSPE is persistent infx with measles variant that can't replicate, is almost gone from US since immunizations for measles are widespread
--AIDS caused by HIV

FIVE HUMAN TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES (slow dz)
1) kuru, caused by handling/ingesting brain tissue
2) CJD = Creutzfeldt-Jakob dz, iatrogenic trans by corneal transplant, brain electrodes, growth hormone, also genetic and sporadic
3) variant CJD seems to be caused by eating "mad cow" meat
4) Gerstmann-Straussler-Scheinker syndrome (GSS) caused by germ cell mutation
5) fatal familial insomnia caused by germ cell mutation

SLOW DISEASES OF ANIMALS
--scrapie and visna in sheep (visna is viral)
--BSE = bovine spongiform encephalopathy in cows (mad cow)
--chronic wastine disease in deeer and elk