Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery.

Rabies virus (RABV) is a neurotropic virus that depends on long distance axonal transport in order to reach the central nervous system (CNS). The strategy RABV uses to hijack the cellular transport machinery is still not clear. It is thought that RABV interacts with membrane receptors in order to in...

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Autores principales:	Shani Gluska, Eitan Erez Zahavi, Michael Chein, Tal Gradus, Anja Bauer, Stefan Finke, Eran Perlson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b6a634a1cc1643458071df03ce9e48a9
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spelling	oai:doaj.org-article:b6a634a1cc1643458071df03ce9e48a92021-11-25T05:46:08ZRabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery.1553-73661553-737410.1371/journal.ppat.1004348https://doaj.org/article/b6a634a1cc1643458071df03ce9e48a92014-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25165859/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Rabies virus (RABV) is a neurotropic virus that depends on long distance axonal transport in order to reach the central nervous system (CNS). The strategy RABV uses to hijack the cellular transport machinery is still not clear. It is thought that RABV interacts with membrane receptors in order to internalize and exploit the endosomal trafficking pathway, yet this has never been demonstrated directly. The p75 Nerve Growth Factor (NGF) receptor (p75NTR) binds RABV Glycoprotein (RABV-G) with high affinity. However, as p75NTR is not essential for RABV infection, the specific role of this interaction remains in question. Here we used live cell imaging to track RABV entry at nerve terminals and studied its retrograde transport along the axon with and without the p75NTR receptor. First, we found that NGF, an endogenous p75NTR ligand, and RABV, are localized in corresponding domains along nerve tips. RABV and NGF were internalized at similar time frames, suggesting comparable entry machineries. Next, we demonstrated that RABV could internalize together with p75NTR. Characterizing RABV retrograde movement along the axon, we showed the virus is transported in acidic compartments, mostly with p75NTR. Interestingly, RABV is transported faster than NGF, suggesting that RABV not only hijacks the transport machinery but can also manipulate it. Co-transport of RABV and NGF identified two modes of transport, slow and fast, that may represent a differential control of the trafficking machinery by RABV. Finally, we determined that p75NTR-dependent transport of RABV is faster and more directed than p75NTR-independent RABV transport. This fast route to the neuronal cell body is characterized by both an increase in instantaneous velocities and fewer, shorter stops en route. Hence, RABV may employ p75NTR-dependent transport as a fast mechanism to facilitate movement to the CNS.Shani GluskaEitan Erez ZahaviMichael CheinTal GradusAnja BauerStefan FinkeEran PerlsonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 8, p e1004348 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Shani Gluska Eitan Erez Zahavi Michael Chein Tal Gradus Anja Bauer Stefan Finke Eran Perlson Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery.
description	Rabies virus (RABV) is a neurotropic virus that depends on long distance axonal transport in order to reach the central nervous system (CNS). The strategy RABV uses to hijack the cellular transport machinery is still not clear. It is thought that RABV interacts with membrane receptors in order to internalize and exploit the endosomal trafficking pathway, yet this has never been demonstrated directly. The p75 Nerve Growth Factor (NGF) receptor (p75NTR) binds RABV Glycoprotein (RABV-G) with high affinity. However, as p75NTR is not essential for RABV infection, the specific role of this interaction remains in question. Here we used live cell imaging to track RABV entry at nerve terminals and studied its retrograde transport along the axon with and without the p75NTR receptor. First, we found that NGF, an endogenous p75NTR ligand, and RABV, are localized in corresponding domains along nerve tips. RABV and NGF were internalized at similar time frames, suggesting comparable entry machineries. Next, we demonstrated that RABV could internalize together with p75NTR. Characterizing RABV retrograde movement along the axon, we showed the virus is transported in acidic compartments, mostly with p75NTR. Interestingly, RABV is transported faster than NGF, suggesting that RABV not only hijacks the transport machinery but can also manipulate it. Co-transport of RABV and NGF identified two modes of transport, slow and fast, that may represent a differential control of the trafficking machinery by RABV. Finally, we determined that p75NTR-dependent transport of RABV is faster and more directed than p75NTR-independent RABV transport. This fast route to the neuronal cell body is characterized by both an increase in instantaneous velocities and fewer, shorter stops en route. Hence, RABV may employ p75NTR-dependent transport as a fast mechanism to facilitate movement to the CNS.
format	article
author	Shani Gluska Eitan Erez Zahavi Michael Chein Tal Gradus Anja Bauer Stefan Finke Eran Perlson
author_facet	Shani Gluska Eitan Erez Zahavi Michael Chein Tal Gradus Anja Bauer Stefan Finke Eran Perlson
author_sort	Shani Gluska
title	Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery.
title_short	Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery.
title_full	Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery.
title_fullStr	Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery.
title_full_unstemmed	Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery.
title_sort	rabies virus hijacks and accelerates the p75ntr retrograde axonal transport machinery.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/b6a634a1cc1643458071df03ce9e48a9
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Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery.

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