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.
journal_name
Sci Signaljournal_title
Science signalingauthors
Préhaud C,Wolff N,Terrien E,Lafage M,Mégret F,Babault N,Cordier F,Tan GS,Maitrepierre E,Ménager P,Chopy D,Hoos S,England P,Delepierre M,Schnell MJ,Buc H,Lafon Mdoi
10.1126/scisignal.2000510subject
Has Abstractpub_date
2010-01-19 00:00:00pages
ra5issue
105eissn
1945-0877issn
1937-9145pii
3/105/ra5journal_volume
3pub_type
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