IMMUNOBIOLOGY OF SCRAPIE VIRUS INFECTION

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Scrapie is a naturally occurring spongiform encephalopathy of sheep and goats which cause clinically and pathological changes similar to those of Creutzfeld-Jakob and Kuru diseases of man. A unique protein called prion protein (PrP) has been found to be a major component of purified samples of scrapie infectivity and is believed by some people to be the actual infectious agent. We previously isolated two cDNA clones of the PrP mRNA from acrapie-infected mouse brain. In the past year, we have finished determining the complete sequence of these mouse prion protein cDNAs. Comparison of the sequence with that of hamster PrP indicated that these very homologous genes showed nearly equivalent evolutinary divergence in both their coding and noncoding regions which confirmed previous findings that the PrP genes are normal endogenous genes of many species rather than genes of an exogenous infectious agent. The possibility that post-translational modification of the endogenous gene product results in creation of the infectious scrapie agent has not been completely excluded. Although several attempts have been made to adapt the scrapie agent to in vitro growth, the few positive cultures reported have been of low titer. Nevertheless, adaptation of the agent to cell culture could permit detailed characterization of the agent and offer the possibility of in vitro titrations and a marked reduction in bioassay related problems. Toward this goal neuroblastoma cell lines of mouse origin were successfully infected with scrapie agent. Infected cultures were maintained through 21 passages, well beyond the number needed to assure that replication had occurred. Infection appeared to be species-specific in that agent derived from hamster brain did not infect the mouse derived neuroblastoma cell lines. Cells from currently infected cultures were cloned in hopes of increasing infectivity levels and additional cell lines are being analyzed in anticipation that others even more receptive to scrapie might be identified.