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

文献类型： 外文期刊

第一作者： Wang, Jinliang

作者： Wang, Jinliang;Wang, Zilong;Liu, Renqiang;Shuai, Lei;Wang, Xinxin;Luo, Jie;Wang, Chong;Chen, Weiye;Wang, Xijun;Ge, Jinying;He, Xijun;Wen, Zhiyuan;Bu, Zhigao;Bu, Zhigao

作者机构：

期刊名称：PLOS PATHOGENS （ 影响因子：6.823； 五年影响因子：7.455 ）

ISSN： 1553-7366

年卷期： 2018 年 14 卷 7 期

页码：

收录情况： SCI

摘要： 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 knockdown 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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