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Journal of Virology, December 2007, p. 13794-13800, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01502-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Prion Strain- and Species-Dependent Effects of Antiprion Molecules in Primary Neuronal Cultures{triangledown}

Sabrina Cronier,1,{dagger} Vincent Beringue,1 Anne Bellon,1,2,{ddagger} Jean-Michel Peyrin,1* and Hubert Laude1*

Unité de Virologie Immunologie Moléculaires, INRA, 78350 Jouy-en-Josas, France,1 Virology Department, Preclinical Research and Development, CSL Behring, Marburg, Germany2

Received 10 July 2007/ Accepted 20 September 2007

Transmissible spongiform encephalopathies (TSE) arise as a consequence of infection of the central nervous system by prions and are incurable. To date, most antiprion compounds identified by in vitro screening failed to exhibit therapeutic activity in animals, thus calling for new assays that could more accurately predict their in vivo potency. Primary nerve cell cultures are routinely used to assess neurotoxicity of chemical compounds. Here, we report that prion strains from different species can propagate in primary neuronal cultures derived from transgenic mouse lines overexpressing ovine, murine, hamster, or human prion protein. Using this newly developed cell system, the activity of three generic compounds known to cure prion-infected cell lines was evaluated. We show that the antiprion activity observed in neuronal cultures is species or strain dependent and recapitulates to some extent the activity reported in vivo in rodent models. Therefore, infected primary neuronal cultures may be a relevant system in which to investigate the efficacy and mode of action of antiprion drugs, including toward human transmissible spongiform encephalopathy agents.

* Corresponding author. Mailing address: INRA, Virologie Immunologie Moléculaires, 78350 Jouy-en-Josas, France. Phone: 33 1 3465 2600. Fax: 33 1 3465 2621. E-mail for Jean-Michel Peyrin: jean-michel.peyrin{at}jouy.inra.fr. E-mail for Hubert Laude: hubert.laude{at}jouy.inra.fr

{triangledown} Published ahead of print on 3 October 2007.

{dagger} Present address: MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom.

{ddagger} Present address: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037.

Journal of Virology, December 2007, p. 13794-13800, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01502-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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