Kinetics of infectivity are dissociated from PrP accumulation in salivary glands of Creutzfeldt-Jakob disease agent-inoculated mice

Abstract

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.