Attenuation of rabies virulence: takeover by the cytoplasmic domain of its envelope protein. - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue Science Signaling Année : 2010

Attenuation of rabies virulence: takeover by the cytoplasmic domain of its envelope protein.

Monique Lafon
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Résumé

The capacity of a rabies virus to promote neuronal survival (a signature of virulence) or death (a marker of attenuation) depends on the cellular partners recruited by the PDZ-binding site (PDZ-BS) of its envelope glycoprotein (G). Neuronal survival requires the selective association of the PDZ-BS of G with the PDZ domains of two closely related serine-threonine kinases, MAST1 and MAST2. Here, we found that a single amino acid change in the PDZ-BS triggered the apoptotic death of infected neurons and enabled G to interact with additional PDZ partners, in particular the tyrosine phosphatase PTPN4. Knockdown of PTPN4 abrogated virus-mediated apoptosis. Thus, we propose that attenuation of rabies virus requires expansion of the set of host PDZ proteins with which G interacts, which interferes with the finely tuned homeostasis required for survival of the infected neuron.
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Dates et versions

pasteur-00460584 , version 1 (01-03-2010)

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Christophe Préhaud, Nicolas Wolff, Elouan Terrien, Mireille Lafage, Françoise Mégret, et al.. Attenuation of rabies virulence: takeover by the cytoplasmic domain of its envelope protein.. Science Signaling, 2010, 3 (105), pp.ra5. ⟨10.1126/scisignal.2000510⟩. ⟨pasteur-00460584⟩

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