Experimental transmission of distinct human CJD agents
- Transmissions of human sporadic CJD (sCJD) to small laboratory animals (guinea pigs, hamsters, mice) (23-25). Previously, it was believed that human CJD and kuru agents could only infect primates. Experimental rodents reproduced typical TSE lesions of humans, and the sCJD agent was unlike any sheep scrapie strain.
- Infection is first spread by white blood cells to the lymphoreticular tissues, a typical viral route (26,27).
- Positive CJD transmission from cornea inoculated into the eye (28). This study also underscored the potential for inadvertent iatrogenic infections.
- No maternal transmission from infected parent guinea pigs for 12 years, i.e., agent is not germline (29)
- sCJD agent and Asiatic CJD agents are markedly different, implicating environment-specific source (30)
- TSE agents show conserved identities after passage through different species, and are not host-encoded (30)
- Cultures derived from infected animals, or cells exposed to infectious material, can become transformed, and can also cause huge tumors in nude mice (31-33).
HUMAN TSE STRAINs: Sporadic sCJD in normal mice elicits only small localized PrP deposits (red) in the thalamus after a very long incubation of >420 days (left). In contrast, Asiatic isolates such as FU-CJD (right) rapidly induce widespread PrP deposits.