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

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 Signal

journal_title

Science signaling

authors

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 M

doi

10.1126/scisignal.2000510

subject

Has Abstract

pub_date

2010-01-19 00:00:00

pages

ra5

issue

105

eissn

1945-0877

issn

1937-9145

pii

3/105/ra5

journal_volume

3

pub_type

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