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

Sci Signal. 2010 Jan 19;3(105):ra5. doi: 10.1126/scisignal.2000510.

Christophe Préhaud ¹, Nicolas Wolff, Elouan Terrien, Mireille Lafage, Françoise Mégret, Nicolas Babault, Florence Cordier, Gene S Tan, Elodie Maitrepierre, Pauline Ménager, Damien Chopy, Sylviane Hoos, Patrick England, Muriel Delepierre, Matthias J Schnell, Henri Buc, Monique Lafon

Affiliations

Affiliation

1 Institut Pasteur, 75724 Paris, France.

PMID: 20086240 DOI: 10.1126/scisignal.2000510

Abstract

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.

Name
Email *

	Sorry, but the email address you supplied was invalid.