Table I. Comparison of different TSE agents.

Key features of different TSE agents propagated in mice with wt PrP. The country of origin, original species and diagnosis are listed. One or more + signs indicates the agent was passaged in non-murine species before being transmitted to mice. Thus SY-CJD was passaged in guinea pigs and hamsters before being transmitted to mice [Manuelidis et al., 1978] whereas the other human CJD homogenates were transmitted directly to mice [Manuelidis et al., 1988]. Nevertheless, the prolonged incubation time, even after ≧3 passages in CD-1 mice, was diagnostic for the sCJD agent, as were the very restricted medial thalamic lesions. In contrast, the geographic isolates from Japan were markedly different, with rapid incubation times and widespread spongiform lesions, even though they showed the same Type I PrP-res banding pattern as sCJD [Manuelidis, 1998; Manuelidis et al., 2000]. FU-CJD was first passaged in rats before being transmitted to mice, but is indistinguishable from YAM-CJD, i.e., shows comparable stability as the sCJD agent that is independent of species PrP. Only the vCJD and BSE agents produced Type 2 PrP-res (with the 19kd diagnostic marker) in brain. The mutant 263K scrapie agent, repeatedly cloned at limiting dilution, passaged in five different species and further selected for its low pathogenicity in mice where it gave inapparent infection for >600 days [Kimberlin et al., 1989]. Yet it still yielded the standard Type I PrP-res profile (see Fig. 3) even though its biological properties were changed profoundly. It has a much more prolonged mouse incubation time than the other scrapie agents, even after serial passage, and induces a different distribution of brain pathology than any of the other agents (data not shown).

	Country: original species	Diagnosis	Agent name	Incubation in CD-1 mice ≥p3	Mo. brain pathology	Mo. brain PrP-res
1	USA: human (++)	sCJD	SY-CJD	380 days	very restriicted	Type 1
2	Italy: human	sCJD	LU-CJD	360 days	very restriicted	Type 1
3	UK: human	GSS	MA-CJD	380 days	very restriicted	Type 1
4	Japan: human (+)	GSS	FU-CJD	120 days	diffuse	Type 1
5	Japan: human	GSS	YAM-CJD	130 days	diffuse	Type 1
6	UK: human	vCJD	vCJD	170 days	BSE	Type 2
7	UK: cow	BSE	BSE	160 days*	BSE	Ty-2 (& primate)
8	UK: sheep	scrapie	22L Sc	140 days	Scrapie variant	Type 1
9	UK: sheep	scrapie	Ch (RML)-Sc	120 days	Scrapie variant	Type 1
10	UK: sheep (++++)	scrapie	263K-Sc	330 days	263K	Type 1

^*BSE was propagated from a sick UK cow brain by N. Nishida in Japan using ddY mice and at 2^nd passage had the same incubation time as vCJD. BSE brain also showed the same lesion distribution as seen in vCJD brain (see text and Fig. 2A). Incubation time comparisons are all based on mice inoculated with 1% brain homogenates and PrP-res band differences in GT1 cells infected with these different agents are shown in Fig. 4.