Attenuation of rabies virulence: takeover by the cytoplasmic domain of its envelope protein.
Publication/Presentation Date
1-19-2010
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.
Volume
3
Issue
105
First Page
5
Last Page
5
ISSN
1937-9145
Published In/Presented At
Préhaud, C., Wolff, N., Terrien, E., Lafage, M., Mégret, F., Babault, N., Cordier, F., Tan, G. S., Maitrepierre, E., Ménager, P., Chopy, D., Hoos, S., England, P., Delepierre, M., Schnell, M. J., Buc, H., & Lafon, M. (2010). Attenuation of rabies virulence: takeover by the cytoplasmic domain of its envelope protein. Science signaling, 3(105), ra5. https://doi.org/10.1126/scisignal.2000510
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
20086240
Department(s)
Administration and Leadership
Document Type
Article