LCMV glycosylation modulates viral fitness and cell tropism.
LCMV glycosylation modulates viral fitness and cell tropism.
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DOI：
10.1371/journal.pone.0053273
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Buchmeier MJ
中科院分区：
文献类型：
--
作者：
Bonhomme CJ;Knopp KA;Bederka LH;Angelini MM;Buchmeier MJ
沙粒病毒的糖蛋白 (GP) 在 11 个保守的 N-糖基化位点被糖基化。我们构建了重组淋巴细胞脉络膜脑膜炎病毒 (rLCMV)，其特征是添加或删除了这些 N-聚糖，以研究它们在病毒生命周期中的作用。两个位点（T87 和 S97）的 N-糖基化被发现对于拯救 rLCMV 是必要的。 9 个突变体中的 3 个在上皮细胞、神经元细胞或巨噬细胞细胞中的选择性压力下成功拯救突变体 S116A、T234A 和 S373A，恢复为 WT 序列。在七个稳定的 N-聚糖缺失突变体中，其中五个导致病毒适应性和细胞向性改变，评估为小鼠原代皮质神经元或骨髓来源的巨噬细胞的生长。这些结果表明，LCMV GP 中 N-聚糖的缺失可能赋予病毒感染神经元的优势，但对巨噬细胞的感染却不利。
The glycoprotein (GP) of arenaviruses is glycosylated at 11 conserved N-glycosylation sites. We constructed recombinant lymphocytic choriomeningitis virus (rLCMV) featuring either additions or deletions of these N-glycans to investigate their role in the viral life cycle. N-glycosylation at two sites, T87 and S97, were found to be necessary to rescue rLCMV. Three of nine successfully rescued mutants, S116A, T234A, and S373A, under selective pressures in either epithelial, neuronal, or macrophage cells reverted to WT sequence. Of the seven stable N-glycan deletion mutants, five of these led to altered viral fitness and cell tropism, assessed as growth in either mouse primary cortical neurons or bone marrow derived macrophages. These results demonstrate that the deletion of N-glycans in LCMV GP may confer an advantage to the virus for infection of neurons but a disadvantage in macrophages.