Metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus

PLoS Pathogens
Jinliang WangZhigao Bu

Abstract

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.

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Citations

Nov 2, 2019·Journal of Virology·Lei ShuaiZhigao Bu
Mar 10, 2020·PLoS Pathogens·Laura BelotAurélie A Albertini
Apr 24, 2020·Journal of Virology·Venice Du PontRichard K Plemper
Jun 10, 2020·Genes, Brain, and Behavior·Richard Lathe, David St Clair
Jun 5, 2020·Journal of Virology·Wenqiang WangGuan-Zhu Han
May 30, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jun LuoXiaofeng Guo
Nov 20, 2020·Viruses·Alexis Duvergé, Matteo Negroni
Apr 4, 2021·Journal of the Neurological Sciences·Pasin Hemachudha, Thiravat Hemachudha
Jul 3, 2021·International Journal of Molecular Sciences·Valeria De PasqualeLuigi Michele Pavone
Jul 5, 2021·Iranian Biomedical Journal·Fatemeh ZandiBehrouz Vaziri
Jul 24, 2021·Scientific Reports·Zih-Ting ChangYu-Shin Nai
Oct 29, 2021·Frontiers in Cellular and Infection Microbiology·Manar E KhalifaMuhammad Munir

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Methods Mentioned

BETA
flow cytometry
transfection
co-immunoprecipitation
pull-down
co-IP
pulled down
FCS
PCR

Software Mentioned

Columbus
GraphPad Prism
Bitplane Imaris
FlowJo
Imaris

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