Rabies, caused by rabies virus (RABV), is a zoonotic disease infecting mammals including humans. Studies have confirmed that glycoprotein (G) is most related to RABV pathogenicity. In the present study, to discover more amino acid sites related to viral pathogenicity, artificial mutants have been constructed in G of virulent strain GD-SH-01 backbone. Results showed that pathogenicity of GD-SH-01 significantly decreased when Gly349 was replaced by Glu349 through in vivo assays. Gly349→Glu349 of G did not significantly influence viral growth and spread in NA cells. Gly349→Glu349 of G increased the immunogenicity of GD-SH-01 in periphery and induced more expression of interferon alpha (IFN-α) in the brain in mice. It was observed that Gly349→Glu349 of G led to enhanced blood-brain barrier (BBB) permeability at day 5 postinfection. All together, these data revealed that Gly349→Glu349 of G mutation decreased RABV pathogenicity through enhanced immune response and increased BBB permeability. This study provides a new referenced site G349 that could attenuate pathogenicity of RABV.

中文翻译：

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糖蛋白349位的氨基酸突变影响狂犬病病毒的致病性。

由狂犬病病毒（RABV）引起的狂犬病是一种人畜共患疾病，可感染包括人类在内的哺乳动物。研究证实糖蛋白（G）与RABV致病性最相关。在本研究中，为发现更多与病毒致病性有关的氨基酸位点，在有毒力的菌株GD-SH-01主链的G中构建了人工突变体。结果表明，通过体内试验将Gly349替换为Gly349后，GD-SH-01的致病性大大降低。G的Gly349→Glu349没有显着影响病毒的生长和在NA细胞中的扩散。G的Gly349→Glu349增加了小鼠外周血GD-SH-01的免疫原性，并诱导了小鼠脑内干扰素α（IFN-α）的更多表达。观察到G的Gly349→Glu349在感染后第5天导致血脑屏障（BBB）通透性增强。全部一起，这些数据表明，G突变的Gly349→Glu349通过增强免疫应答和增加BBB通透性降低了RABV的致病性。这项研究提供了一个新的参考位点G349，可以减弱RABV的致病性。