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The rabies virus glycoprotein receptor p75(NTR) is not essential for rabies virus infection

Tuffereau, C; Schmidt, K; Langevin, C; Lafay, F; Dechant, G; Koltzenburg, M; (2007) The rabies virus glycoprotein receptor p75(NTR) is not essential for rabies virus infection. J VIROL , 81 (24) 13622 - 13630. 10.1128/JVI.02368-06.

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Abstract

Rabies virus glycoprotein (RVG) is known to be the only factor that mediates rabies infection. The neurotrophin receptor (p75(NTR)), through its cysteine-rich domain 1, is a specific receptor for RVG and neutralizes virus infectivity, but its role in virus infection has remained obscure. We used adult mouse dorsal root ganglion (DRG) neurons as a model to study the role of p75NTR in RV infection of primary neurons. We show that RV infects around 20% of DRG neurons, of which more than 80% are p75NTR positive, have large diameters, and are capsaicin insensitive. Surprisingly, RV binding and infection are absent in about half of the p75(NTR)-expressing DRG neurons which have small diameters and are often capsaicin sensitive. This indicates that p75(NTR) is not sufficient to mediate RV interaction in sensory neurons. The rate and specificity of neural infection are unchanged in RV-infected p75(NTRExon-/-) mice that lack all extracellular receptor domains and in wild-type mice infected with two independent RV mutants that lack p75NTR binding. Accordingly, the mortality rate is unchanged in the absence of RV-p75(NTR) interaction. We conclude that although p75NTR is a receptor for soluble RVG in transfected cells of heterologous expression systems, an RVG-p75(NTR) interaction is not necessary for RV infection of primary neurons. This means that other receptors are required to mediate RV infection in vivo and in vitro.

Type: Article
Title: The rabies virus glycoprotein receptor p75(NTR) is not essential for rabies virus infection
DOI: 10.1128/JVI.02368-06
Keywords: NERVE-GROWTH-FACTOR, P75 NEUROTROPHIN RECEPTOR, DORSAL-ROOT GANGLIA, MYELIN-ASSOCIATED GLYCOPROTEIN, SENSORY NEURONS, NOGO-RECEPTOR, ACETYLCHOLINE-RECEPTOR, TRANSNEURONAL TRACER, NOCICEPTIVE NEURONS, CAPSAICIN RECEPTOR
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: http://discovery.ucl.ac.uk/id/eprint/126417
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