Deficient Incorporation of Rabies Virus Glycoprotein into Virions Enhances Virus-Induced Immune Evasion and Viral Pathogenicity
Deficient Incorporation of Rabies Virus Glycoprotein into Virions Enhances Virus-Induced Immune Evasion and Viral Pathogenicity
复制标题
狂犬病病毒糖蛋白与病毒粒子的掺入不足会增强病毒诱导的免疫逃避和病毒致病性
DOI：
10.3390/v11030218
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发表时间：
2019-03-04
期刊：
影响因子：
4.7
通讯作者：
Yang, Yang
中科院分区：
文献类型：
--
作者：
Li, Chunfu;Zhang, Hongliang;Yang, Yang
先前的研究表明，野生型（wt）狂犬病毒（RABV）通过限制糖蛋白(G)的表达来逃避宿主的免疫反应，糖蛋白(G)可以阻断树突状细胞（dc）的激活并诱导病毒中和抗体（VNAs）的产生。在本研究中，与实验室适应的病毒相比，wt rabv不仅限制了G的表达，而且减少了G进入成熟病毒粒子的结合。使用表达三重G的重组RABV进一步确定G的表达是否与掺入有关。与表达单个G拷贝的病毒相比，重组病毒G的表达和结合更高，激活的DC更多。使用枯草菌素或二硫苏糖醇(DTT)/ Nonidet P-40 （NP40）去除G几乎完全消除DC激活和VNA的产生。因此，这些缺乏g的病毒在小鼠中引起致命感染。因此，wt rabv可以破坏dc诱导的抗病毒免疫反应，并通过降低感染细胞中的G表达和G并入病毒粒子来维持致病性。
Previous studies have shown that wild-type (wt) rabies virus (RABV) evades the host immune response by restricting expression of glycoprotein (G), which blocks activation of dendritic cells (DCs) and induces production of virus-neutralizing antibodies (VNAs). In the present study, wt RABVs not only restricted G expression but also reduced incorporation of G into mature virions compared with laboratory-adapted viruses. A recombinant RABV expressing triple G was used to further determine whether G expression relates to incorporation. The recombinant virus showed higher expression and incorporation of G and activated more DCs than the virus that expressed a single copy of G. Removal of G from viruses using subtilisin or Dithiothreitol (DTT)/ Nonidet P-40 (NP40) almost completely abolishes DC activation and VNA production. Consequently, these G-depleted viruses cause lethal infection in mice. Thus, wt RABVs can subvert DC-induced antiviral immune response and maintain pathogenicity by decreasing G expression in infected cells and G incorporation into virions.