Metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus.
Rabies virus (RABV) invades the central nervous system and nearly always causes fatal disease in humans. How RABV interacts with host neuron membrane receptors to become internalized and cause rabid symptoms is not yet fully understood. Here, we identified a novel receptor of RABV, which RABV uses t...
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2018-07-01
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doaj-de6c31ce7c33423ca72e3ec4ce4564482020-11-25T01:32:47ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742018-07-01147e100718910.1371/journal.ppat.1007189Metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus.Jinliang WangZilong WangRenqiang LiuLei ShuaiXinxin WangJie LuoChong WangWeiye ChenXijun WangJinying GeXijun HeZhiyuan WenZhigao BuRabies virus (RABV) invades the central nervous system and nearly always causes fatal disease in humans. How RABV interacts with host neuron membrane receptors to become internalized and cause rabid symptoms is not yet fully understood. Here, we identified a novel receptor of RABV, which RABV uses to infect neurons. We found that metabotropic glutamate receptor subtype 2 (mGluR2), a member of the G protein-coupled receptor family that is abundant in the central nervous system, directly interacts with RABV glycoprotein to mediate virus entry. RABV infection was drastically decreased after mGluR2 siRNA knock-down in cells. Antibodies to mGluR2 blocked RABV infection in cells in vitro. Moreover, mGluR2 ectodomain soluble protein neutralized the infectivity of RABV cell-adapted strains and a street strain in cells (in vitro) and in mice (in vivo). We further found that RABV and mGluR2 are internalized into cells and transported to early and late endosomes together. These results suggest that mGluR2 is a functional cellular entry receptor for RABV. Our findings may open a door to explore and understand the neuropathogenesis of rabies.http://europepmc.org/articles/PMC6070288?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jinliang Wang Zilong Wang Renqiang Liu Lei Shuai Xinxin Wang Jie Luo Chong Wang Weiye Chen Xijun Wang Jinying Ge Xijun He Zhiyuan Wen Zhigao Bu |
spellingShingle |
Jinliang Wang Zilong Wang Renqiang Liu Lei Shuai Xinxin Wang Jie Luo Chong Wang Weiye Chen Xijun Wang Jinying Ge Xijun He Zhiyuan Wen Zhigao Bu Metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus. PLoS Pathogens |
author_facet |
Jinliang Wang Zilong Wang Renqiang Liu Lei Shuai Xinxin Wang Jie Luo Chong Wang Weiye Chen Xijun Wang Jinying Ge Xijun He Zhiyuan Wen Zhigao Bu |
author_sort |
Jinliang Wang |
title |
Metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus. |
title_short |
Metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus. |
title_full |
Metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus. |
title_fullStr |
Metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus. |
title_full_unstemmed |
Metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus. |
title_sort |
metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2018-07-01 |
description |
Rabies virus (RABV) invades the central nervous system and nearly always causes fatal disease in humans. How RABV interacts with host neuron membrane receptors to become internalized and cause rabid symptoms is not yet fully understood. Here, we identified a novel receptor of RABV, which RABV uses to infect neurons. We found that metabotropic glutamate receptor subtype 2 (mGluR2), a member of the G protein-coupled receptor family that is abundant in the central nervous system, directly interacts with RABV glycoprotein to mediate virus entry. RABV infection was drastically decreased after mGluR2 siRNA knock-down in cells. Antibodies to mGluR2 blocked RABV infection in cells in vitro. Moreover, mGluR2 ectodomain soluble protein neutralized the infectivity of RABV cell-adapted strains and a street strain in cells (in vitro) and in mice (in vivo). We further found that RABV and mGluR2 are internalized into cells and transported to early and late endosomes together. These results suggest that mGluR2 is a functional cellular entry receptor for RABV. Our findings may open a door to explore and understand the neuropathogenesis of rabies. |
url |
http://europepmc.org/articles/PMC6070288?pdf=render |
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