天然衣壳变体的结构和功能分析表明 BK 多瘤病毒的非依赖唾液酸进入方式。
Structural and functional analysis of natural capsid variants suggests sialic acid-independent entry of BK polyomavirus.
机构信息
Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France; Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Glycoscience Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
出版信息
Cell Rep. 2023 Feb 28;42(2):112114. doi: 10.1016/j.celrep.2023.112114. Epub 2023 Feb 14.
BK polyomavirus (BKPyV) is an opportunistic pathogen that uses the b-series gangliosides GD1b and GT1b as entry receptors. Here, we characterize the impact of naturally occurring VP1 mutations on ganglioside binding, VP1 protein structure, and virus tropism. Infectious entry of single mutants E73Q and E73A and the triple mutant A72V-E73Q-E82Q (VQQ) remains sialic acid dependent, and all three variants acquire binding to a-series gangliosides, including GD1a. However, the E73A and VQQ variants lose the ability to infect ganglioside-complemented cells, and this correlates with a clear shift of the BC2 loop in the crystal structures of E73A and VQQ. On the other hand, the K69N mutation in the K69N-E82Q variant leads to a steric clash that precludes sialic acid binding. Nevertheless, this mutant retains significant infectivity in 293TT cells, which is not dependent on heparan sulfate proteoglycans, implying that an unknown sialic acid-independent entry receptor for BKPyV exists.
BK 多瘤病毒（BKPyV）是一种机会性病原体，它使用 b 系列神经节苷脂 GD1b 和 GT1b 作为进入受体。在这里，我们描述了 VP1 突变对神经节苷脂结合、VP1 蛋白结构和病毒嗜性的影响。单突变体 E73Q 和 E73A 以及三突变体 A72V-E73Q-E82Q（VQQ）的感染性进入仍然依赖唾液酸，并且所有三种变体都获得了与 a 系列神经节苷脂的结合能力，包括 GD1a。然而，E73A 和 VQQ 变体失去了感染神经节苷脂互补细胞的能力，这与 E73A 和 VQQ 的晶体结构中 BC2 环的明显移位相关。另一方面，K69N-E82Q 变体中的 K69N 突变导致空间位阻，从而阻止了唾液酸的结合。然而，该突变体在 293TT 细胞中仍然保持着显著的感染性，这并不依赖于硫酸乙酰肝素蛋白聚糖，这意味着 BKPyV 存在未知的、不依赖于唾液酸的进入受体。
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