Structural heterogeneity of a human norovirus vaccine candidate
Structural heterogeneity of a human norovirus vaccine candidate
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DOI：
10.1016/j.virol.2020.10.005
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发表时间：
2021-01-15
期刊：
影响因子：
3.7
通讯作者：
Hansman, Grant S.
中科院分区：
文献类型：
--
作者：
Devant, Jessica M.;Hansman, Grant S.
人诺如病毒病毒样颗粒（VLP）被认为在形态学和抗原性上与病毒粒子相似。诺如病毒病毒粒子由180个拷贝的衣壳蛋白（VP1）组装而成，并表现出T = 3的二十面体对称性。在这项研究中，我们发现候选疫苗GII.4c VP1形成T = 1和T = 3 VLP，但主要组装成由240个VP1拷贝组成的T = 4二十面体颗粒。相比之下，另一个临床上重要的基因型，GII.17，几乎完全折叠成T = 3 VLP。有趣的是，GII.4c T = 1颗粒与诺如病毒特异性纳米抗体的结合能力高于与GII.4c T = 3和T = 4颗粒的结合能力。我们的数据表明，与较大的T = 3和T = 4颗粒相比，T = 1颗粒上的封闭的纳米抗体结合表位更容易接近。总体而言，该新数据显示GII.4c VLP偏好形成T = 4二十面体对称性，并且在检查抗原性时，对不同大小的诺瓦克病毒VLP的未来研究应谨慎。
Human norovirus virus-like particles (VLPs) are assumed to be morphologically and antigenically similar to virion particles. The norovirus virion is assembled from 180 copies of the capsid protein (VP1) and exhibits T = 3 icosahedral symmetry. In this study, we showed that the vaccine candidate GII.4c VP1 formed T = 1 and T = 3 VLPs, but mainly assembled into T = 4 icosahedral particles that were composed of 240 VP1 copies. In contrast, another clinically important genotype, GII.17, almost exclusively folded into T = 3 VLPs. Interestingly, the GII.4c T = 1 particles had higher binding capacities to norovirus-specific Nanobodies than to GII.4c T = 3 and T = 4 particles. Our data indicated that the occluded Nanobody-binding epitopes on the T = 1 particles were more accessible compared to the larger T = 3 and T = 4 particles. Overall, this new data revealed that GII.4c VLPs had a preference for forming the T = 4 icosahedral symmetry and future studies with varied sized norovirus VLPs should take caution when examining antigenicity.