Addendum

Abstract

Since the time of submission of this supplement, no major breakthrough has been achieved but the most important data will be reviewed here. The major leitmotiv of the current scrapie research, the irreconcilable views of scrapie agent as “prion” [14] or a “virus” [2], is still at work. Neither formal paper on a positive transmission from mice with spontaneous neurodegenerative disorder (see paragraph: 2.3.8) nor results of mice without PrP (see paragraph: 2.3.8) inoculated with scrapie virus have been published. It was, however, reported that amphotericin B delayed the onset of clinical signs and Prp^sc accumulation in hamster brains but not replication of the 263K strain of scrapie virus [19]. Such a clear dissociation of infectivity titer and Prp^sc level may indicate the Prp^sc is not a part of the virus but, on the same token, it may be more important than replication by itself for the development of disease. Using transgenic mice harboring hamster Prn-p gene (see: paragraph 2.4.2), Hecker et al. [6] reported total block of replication of the murine isolate of scrapie by the 263K (Sc237) strain (hamster) of scrapie virus. In contrast, there was no competition between two hamster strains of scrapie virus inoculated into Syrian hamsters, despite clear differences of incubation period, neuropathology and PrP^sc distribution between them. Furthermore, the sequence of PrP^sc appearance in different brain regions seems to followed neuroanatomical connection between them [6]. Scott et al. [16] arrived at the same conclusions using different experimental approach (see: paragraph 3.7) and provided some evidence that neuron-to-neuron spread of the virus is highly restricted by the function of gene Sinc (or Prn-p). Furthermore, the transport of PrP^sc along the white matter tracts was recently reported [18].