狂犬病病毒糖蛋白中的谷氨酸通过星形胶质细胞感染和干扰素反应参与病毒减毒。

Glu in rabies virus glycoprotein is involved in virus attenuation through astrocyte infection and interferon responses.

作者信息

Itakura Yukari, Tabata Koshiro, Morimoto Kohei, Ito Naoto, Chambaro Herman M, Eguchi Ryota, Otsuguro Ken-Ichi, Hall William W, Orba Yasuko, Sawa Hirofumi, Sasaki Michihito

机构信息

Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido 001-0020, Japan.

Laboratory of Pharmacology, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.

出版信息

iScience. 2022 Mar 22;25(4):104122. doi: 10.1016/j.isci.2022.104122. eCollection 2022 Apr 15.

The amino acid residue at position 333 of the rabies virus (RABV) glycoprotein (G333) is a major determinant of RABV pathogenicity. Virulent RABV strains possess Arg, whereas the attenuated strain HEP-Flury (HEP) possesses Glu. To investigate the potential attenuation mechanism dependent on a single amino acid at G333, comparative analysis was performed between HEP and HEPR mutant with Arg. We examined their respective tropism for astrocytes and the subsequent immune responses in astrocytes. Virus replication and subsequent interferon (IFN) responses in astrocytes infected with HEP were increased compared with HEPR both and . Furthermore, involvement of IFN in the avirulency of HEP was demonstrated in IFN-receptor knockout mice. These results indicate that Glu contributes to RABV attenuation by determining the ability of the virus to infect astrocytes and stimulate subsequent IFN responses.

狂犬病病毒（RABV）糖蛋白第333位氨基酸残基（G333）是RABV致病性的主要决定因素。强毒RABV毒株具有精氨酸，而减毒株HEP-Flury（HEP）具有谷氨酸。为了研究依赖于G333处单个氨基酸的潜在减毒机制，对HEP和具有精氨酸的HEPR突变体进行了比较分析。我们检测了它们对星形胶质细胞的各自嗜性以及星形胶质细胞随后的免疫反应。与HEPR相比，感染HEP的星形胶质细胞中的病毒复制及随后的干扰素（IFN）反应均增强。此外，在干扰素受体敲除小鼠中证明了IFN参与HEP的无毒力。这些结果表明，谷氨酸通过决定病毒感染星形胶质细胞并刺激随后的IFN反应的能力，促成了RABV的减毒。