Interspecies transmission of Creutzfeldt-Jakob disease to Syrian hamsters with reference to clinical syndromes and strains of agent.

Abstract

Experimental Creutzfeldt-Jakob disease was serially transmitted from guinea pigs to Syrian hamsters with 100% incidence, morbidity, and mortality. All animals developed a subacute spongiform virus encephalopathy with neuronal destruction and concomitant astrocytic changes. In the first passage three different clinical syndromes were recorded, each with widely variant incubation times; these results suggested there may be different strains of the Creutzfeldt-Jakob agent, some of which may be partially separated when the agent is passaged from one species to another. Accumulations of neurofilaments in neuronal perikarya and processes and increased lipofuscin were suggestive ofchanges seen insenility and aging.The "subacute spongiform virus encephalopathies" (1), characterized by degeneration of the central nervous system with neuronal loss, sponginess of the tissue (status spongiosus), and astrocytosis without accompanying inflammatory infiltrates, have been traced to unconventional replicating agents. In naturally occurring diseases these agents replicate in species ranging from human beings (kuru and Creutzfeldt-Jakob disease) to mink (transmissible mink encephalopathy) and sheep (scrapie). Because the exact nature of the agents comprising this group is unknown, the relationship between agents isolated from the naturally occurring diseases in different species and propagated in different experimental hosts forms the only basis for their comparison. Serial transmission of Creutzfeldt-Jakob disease of human beings to guinea pigs (2, 3), and more recently to mice (4), has been reported from this laboratory. The present paper reports the serial transmission of experimental Creutzfeldt-Jakob disease from guinea pigs to hamsters. Variations in the incubation periods, clinical syndromes, and histological lesions were observed. These results suggested the existence of different strains of the Creutzfeldt-Jakob agent.Experimental data reported in interspecies transmission of experimental scrapie are compared. MATERIALS AND METHODSThree young golden hamsters weighing 25-35 g were inoculated with 0.05 ml intracerebrally and 0.1 ml intraperitoneally of a 1:10 suspension of brain in physiological saline from two guinea pigs that had developed Creutzfeldt-Jakob disease during the fifth passage of the disease. Both guinea pigs used for inoculation revealed on histological examination the characteristic features of a spongiform virus encephalopathy.For serial transmission, seven healthy hamsters (second passage) were injected with similarly prepared inoculum from a sick hamster of the first passage in the same quantities and routes of inoculation as that used in the first passage. When the hamster of the second passage developed the experimental disease (Table 1), a third group of six hamsters was similarly inoculated. From one sick hamster of the third passage the infection was passaged to six healthy hamsters, and the fourth passage is presently in progress. Routinely, half the brain of the sick hamster was frozen to...

Adaptation and Selection of Prion Protein Strain Conformations following Interspecies Transmission of Transmissible Mink Encephalopathy

“…A model for TSE strain adaptation and selection at the molecular level following interspecies transmission is proposed based on both the current findings of TME transmission to hamsters and previous transmission studies (5,6,19,(20)(21)(22)(23)29). Two events likely occur upon interspecies TSE transmission: (i) TSE strain adaptation involves the conversion of host PrP C to PrP Sc by a donor PrP Sc molecule having a different primary structure (i.e., responsible for the species barrier effect) and (ii) the formation of multiple PrP Sc conformations from a single donor PrP Sc conformation that is responsible for generation of TSE strains.…”

Intra- and Interspecies Interactions between Prion Proteins and Effects of Mutations and Polymorphisms

“…Indeed there is now convincing evidence from interspecies transmission studies in animals (Lasmézas et al, 1996(Lasmézas et al, , 2001Bruce et al, 1997) and transgenic mice (Hill et al, 1997;Scott et al, 1999) that cattle BSE prions have been transmitted to humans (Table 1). Hamsters have not been successfully inoculated with bovine PrP (Bradley and Wilesmith, 1993), and Creutzfeldt-Jakob disease was only serially transmitted to Syrian hamsters via guinea pigs (Manuelidis et al, 1978; Table 1). In the latter case, incubation times varied depending on the CJD strain used.…”

“…g Cutlip et al (1994); Clark et al (1995). h Manuelidis et al (1978). i Bradley and Wilesmith (1993).…”

Prion distribution in hamster lung and brain following intraperitoneal inoculation.

“…This observation, coupled with the fact that bioassays are completed only for animals killed up to 22 months, suggests that additional tissues may harbour infectivity. In addition, interpretation of the negative bioassay results is made difficult by the species barrier, which decreases the sensitivity of the bioassay when the sample is from a different host species than the bioassay host (Barlow & Rennie, 1976 ;Manuelidis et al, 1978 ;Kimberlin et al, 1987 ;Prusiner et al, 1990 ;Kocisko et al, 1995 ;Wells et al, 1998).…”