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Published online on December 11, 2007, 10.1073/pnas.0710054104
PNAS | December 26, 2007 | vol. 104 | no. 52 | 20908-20913
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BIOLOGICAL SCIENCES / MEDICAL SCIENCES
Prion strain discrimination in cell culture: The cell panel assay

Sukhvir P. Mahal*, Christopher A. Baker*, Cheryl A. Demczyk*, Emery W. Smith*, Christian Julius{dagger}, and Charles Weissmann*,{ddagger}

*Department of Infectology, Scripps Florida, 5353 Parkside Drive, Jupiter, FL 33458; and {dagger}Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland

Contributed by Charles Weissmann, October 24, 2007 (received for review February 5, 2007)

Prions are thought to consist mainly or entirely of misfolded PrP, a constitutively expressed host protein. Prions associated with the same PrP sequence may occur in the form of different strains; the strain phenotype is believed to be encoded by the conformation of the PrP. Some cell lines can be persistently infected by prions and, interestingly, show preference for certain strains. We report that a cloned murine neuroblastoma cell population, N2a-PK1, is highly heterogeneous in regard to its susceptibility to RML and 22L prions. Remarkably, sibling subclones may show very different relative susceptibilities to the two strains, indicating that the responses can vary independently. We have assembled four cell lines, N2a-PK1, N2a-R33, LD9 and CAD5, which show widely different responses to prion strains RML, 22L, 301C, and Me7, into a panel that allows their discrimination in vitro within 2 weeks, using the standard scrapie cell assay (SSCA).

standard scrapie cell assay | infectivity | response index | PrP

Freely available online through the PNAS open access option.

Author contributions: S.P.M., C.A.B., and C.W. designed research; S.P.M., C.A.B., C.A.D., and E.W.S. performed research; S.P.M., C.A.B., E.W.S., and C.W. analyzed data; C.J. contributed new reagents; and C.W. wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0710054104/DC1.

{ddagger}To whom correspondence should be addressed. E-mail: charlesw{at}scripps.edu

© 2007 by The National Academy of Sciences of the USA


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Related Commentary in PNAS:

Unraveling prion strains with cell biology and organic chemistry
Adriano Aguzzi
PNAS 2008 105: 11-12. [Extract] [Full Text]  



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A. Aguzzi
Unraveling prion strains with cell biology and organic chemistry
PNAS, January 8, 2008; 105(1): 11 - 12.
[Full Text] [PDF]