KINETICS OF INFECTIVITY ARE DISSOCIATED FROM PRP ACCUMULATION IN SALIVARY-GLANDS OF CREUTZFELDT-JAKOB-DISEASE AGENT-INOCULATED MICE

The protease-resistant isoform of prion protein (PrP) has been implicated in the pathogenesis and transmission of Creutzfeldt-Jakob disease (CJD), scrapie and other related diseases, but the relationship between the infectious agent and PrP awaits elucidation. In the present study, we have examined levels of infectivity together with accumulation of the protease-resistant form of PrP (PrP(CJD)) in various tissues of CJD agent-inoculated mice. Accumulation of PrP(CJD)) occurred only in tissues, including brain, salivary gland and spleen, in which infectivity was readily detectable throughout the course of the experiment. The brain showed the highest levels of both infectivity and PrP(CJD)) accumulation, with well correlated kinetics. On the other hand, the high titres of infectivity detected in salivary gland and spleen early after inoculation of the agent were obviously distinguishable from PrP(CJD). Furthermore, in the salivary gland, the kinetics of infectivity and the accumulation of PrP(CJD) reversed; infectivity declined as PrP(CJD) accumulated in the tissue. Our findings indicate that PrP(CJD)) accumulation is associated with replication of the agent; however, PrP(CJD) is unlikely to be the agent itself.