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Beware the Shape-shifter
Mice as a model

by Alicia P. Gregory

One more question in the list of unknowns about CWD is the prevalence of strains. Viruses can manifest as different strains caused by slight genetic variations that result in different biological properties. Prion diseases appear to have similar variations, evidenced by longer or shorter disease incubation periods and differences in severity of symptoms. But how do strains work in prions—without DNA or RNA?

This was one of the questions Telling tackled in San Francisco with Prusiner. "Our work showed that different strains of prions had subtly different conformational states that appeared to correlate with strain properties. The strain of the agent is somehow enciphered within the conformation [shape] of the prion protein, and that conformation is imparted with a high degree of fidelity from one protein to another."

Photo of Rajgopal Yadavalli, Shawn Browning and Jifeng BianAttacking prions in Telling's lab: (left to right) Rajgopal Yadavalli (a postdoctoral fellow), Shawn Browning (a grad student in the microbiology Ph.D. program) and Jifeng Bian (visiting scientist from Shandong Medical University in China)

But how do you isolate strains of CWD? Telling's program, supported by grants from NIH, focuses on transgenic mice. He has inoculated these mice with CWD, and is in the "wait and see" stage. (The long incubation period means it will take a while for clinical symptoms to develop and his next round of work to begin.) Telling will compare CWD from deer and elk to look for strain-indicating differences in the prions.

"This transgenic animal model is important because, for the first time, we'll be able to test the infectivity of various tissues and bodily fluids," he says. "Is saliva the key to how this disease is transmitted from one animal to the next? We can't tell from infected deer and elk." Telling says. Besides the fact that deer and elk aren't ideal experimental models because of their size and expense, the main problem for scientists is the difficulty of maintaining CWD-free control groups.

In addition to making transgenic mice that are susceptible to deer and elk prions, Telling says one future goal of this work is to make use of transgenic mice that are susceptible to human, sheep and cow prions, a crucial step in identifying how prions jump between species. "This will allow us to explore the most important molecular determinants of the species barrier and prion strains. If, for instance, we saw transmission of CWD into mice that normally respond to human prions, it may indicate the potential for CWD transmission to humans."

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