文章基本信息

标题：Glu 333 in rabies virus glycoprotein is involved in virus attenuation through astrocyte infection and interferon responses
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作者：Yukari Itakura ; Koshiro Tabata ; Kohei Morimoto 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：4
页码：1-17
DOI：10.1016/j.isci.2022.104122
语种：English
出版社：Elsevier
摘要：SummaryThe amino acid residue at position 333 of the rabies virus (RABV) glycoprotein (G333) is a major determinant of RABV pathogenicity. Virulent RABV strains possess Arg333, whereas the attenuated strain HEP-Flury (HEP) possesses Glu333. To investigate the potential attenuation mechanism dependent on a single amino acid at G333, comparative analysis was performed between HEP and HEP333R mutant with Arg333. 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 HEP333R bothin vitroandin vivo. Furthermore, involvement of IFN in the avirulency of HEP was demonstrated in IFN-receptor knockout mice. These results indicate that Glu333contributes to RABV attenuation by determining the ability of the virus to infect astrocytes and stimulate subsequent IFN responses.Graphical abstractDisplay OmittedHighlights•Glu333in G protein is responsible for astrocyte infection with RABV HEP strain•Arg333mutation in G protein decreases astrocyte tropism of RABV HEP•RABV HEP evokes higher IFN responses in astrocytes than HEP with Arg333mutation•Glu333-dependent astrocyte infection is involved in the attenuation of RABV HEPImmunology; Cellular neuroscience; Virology