Internalization of rabies virus glycoprotein differs between pathogenic and attenuated virus strains.
Internalization of rabies virus glycoprotein differs between pathogenic and attenuated virus strains.
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DOI：
10.1099/jgv.0.001935
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发表时间：
2023-12
影响因子：
3.8
通讯作者：
Mankouri, Jamel
中科院分区：
文献类型：
--
作者：
Almasoud, Ibrahim;Charlton, Frank W.;Finke, Stefan;Barr, John N.;Mankouri, Jamel
关键词：
人畜共患狂犬病病毒（RABV）是一种非节段性负义RNA病毒，属于弹状病毒科，是引起狂犬病的最常见病原体。RABV糖蛋白（G）形成从RABV病毒体突出并介导病毒附着、进入和传播的三聚体刺突，并且是RABV发病机制的主要决定因素。存在一系列高致病性的RABV毒株，部分原因是它们能够逃避宿主免疫检测。然而，一些菌株是疾病减毒的，可以通过宿主防御来清除。目前缺乏对菌株变异与发病机制的详细分子理解。在这里，我们揭示了从挑战病毒标准株（CVS-11）和高度减毒疫苗株SAD-B19（SAD）的RABV-G蛋白的运输概况的关键差异。我们表明，CVS-G交通到细胞表面，并通过网格蛋白和胆固醇依赖性内吞途径进行快速内化。相比之下，SAD-G仍然驻留在质膜上，并以明显较慢的速率内化。通过CVS-G和SAD-G的工程杂交，我们表明CVS-G的胞质尾区是这些不同内化谱的关键决定因素。丙氨酸扫描进一步显示CVS-G中的Y 497突变（SAD-G中的H497）可降低内化至SAD-G水平的速率。总之，这些数据揭示了CVS-G和SAD-G蛋白之间新的表型差异，这可能有助于改变体内致病性。
The zoonotic rabies virus (RABV) is a non-segmented negative-sense RNA virus classified within the family Rhabdoviridae, and is the most common aetiological agent responsible for fatal rabies disease. The RABV glycoprotein (G) forms trimeric spikes that protrude from RABV virions and mediate virus attachment, entry and spread, and is a major determinant of RABV pathogenesis. A range of RABV strains exist that are highly pathogenic in part due to their ability to evade host immune detection. However, some strains are disease-attenuated and can be cleared by host defences. A detailed molecular understanding of how strain variation relates to pathogenesis is currently lacking. Here, we reveal key differences in the trafficking profiles of RABV-G proteins from the challenge virus standard strain (CVS-11) and a highly attenuated vaccine strain SAD-B19 (SAD). We show that CVS-G traffics to the cell surface and undergoes rapid internalization through both clathrin- and cholesterol-dependent endocytic pathways. In contrast, SAD-G remains resident at the plasma membrane and internalizes at a significantly slower rate. Through engineering hybrids of CVS-G and SAD-G, we show that the cytoplasmic tail of CVS-G is the key determinant of these different internalization profiles. Alanine scanning further revealed that mutation of Y497 in CVS-G (H497 in SAD-G) could reduce the rate of internalization to SAD-G levels. Together, these data reveal new phenotypic differences between CVS-G and SAD-G proteins that may contribute to altered in vivo pathogenicity.
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影响因子：
3.8
作者：
Müller T;Dietzschold B;Ertl H;Fooks AR;Freuling C;Fehlner-Gardiner C;Kliemt J;Meslin FX;Franka R;Rupprecht CE;Tordo N;Wanderler AI;Kieny MP
通讯作者：
Kieny MP
DOI：
10.1073/pnas.0407289101
发表时间：
2004-11-16
影响因子：
11.1
作者：
Faber, M;Pulmanausahakul, R;Dietzschold, B
通讯作者：
Dietzschold, B
影响因子：
3.2
作者：
Morimoto, K;Foley, HD;Dietzschold, B
通讯作者：
Dietzschold, B
影响因子：
4.8
作者：
Royle, SJ;Bobanovic, LK;Murrell-Lagnado, RD
通讯作者：
Murrell-Lagnado, RD
将EGF和转铁蛋白分选在质膜上，并通过货物特异性信号传导向EEA1富集的内体。
影响因子：
4
作者：
Leonard D;Hayakawa A;Lawe D;Lambright D;Bellve KD;Standley C;Lifshitz LM;Fogarty KE;Corvera S
通讯作者：
Corvera S