Norovirus-like VP1 particles exhibit isolate dependent stability profiles.
Norovirus-like VP1 particles exhibit isolate dependent stability profiles.
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DOI：
10.1088/1361-648x/aaa43b
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发表时间：
2018-02-14
期刊：
影响因子：
--
通讯作者：
Uetrecht C
中科院分区：
文献类型：
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作者：
Pogan R;Schneider C;Reimer R;Hansman G;Uetrecht C
诺如病毒是病毒性胃肠炎的主要病因，新的变种经常出现。有三种诺如病毒基因组感染人类。这些基因组是根据其主要衣壳蛋白的序列划分的，当重组表达时，其能够形成病毒样颗粒（VLP）。已知原型GI. 1诺瓦克病毒的VLP在碱处理后分解成特异性衣壳蛋白寡聚体。在这里，对GI.1和GII.17的变体进行了天然质谱和电子显微镜检查，揭示了这些组之间稳定性的差异。除此之外，这些实验表明，即使在基因型内的变体之间也存在差异。衣壳的稳定性进行了监测，在不同的乙酸铵溶液中变化的离子强度和pH值。调查的GI。1西切斯特分离显示可比拆卸配置文件先前研究的GI。1诺瓦克病毒分离株。然而，观察到的差异与西切斯特更敏感的碱性pH值。在形成鲜明对比的是，属于目前流行的基因组GII的变体的衣壳在所有测试条件下是稳定的。这两种变体已经在中性pH下形成较小的衣壳颗粒。西切斯特相对于诺瓦克病毒的S结构域中的某些氨基酸取代可能导致这些T = 1衣壳的形成。
Noroviruses are the main cause of viral gastroenteritis with new variants emerging frequently. There are three norovirus genogroups infecting humans. These genogroups are divided based on the sequence of their major capsid protein, which is able to form virus-like particles (VLPs) when expressed recombinantly. VLPs of the prototypical GI.1 Norwalk virus are known to disassemble into specific capsid protein oligomers upon alkaline treatment. Here, native mass spectrometry and electron microscopy on variants of GI.1 and of GII.17 were performed, revealing differences in terms of stability between these groups. Beyond that, these experiments indicate differences even between variants within a genotype. The capsid stability was monitored in different ammonium acetate solutions varying both in ionic strength and pH. The investigated GI.1 West Chester isolate showed comparable disassembly profiles to the previously studied GI.1 Norwalk virus isolate. However, differences were observed with the West Chester being more sensitive to alkaline pH. In stark contrast to that, capsids of the variant belonging to the currently prevalent genogroup GII were stable in all tested conditions. Both variants formed smaller capsid particles already at neutral pH. Certain amino acid substitutions in the S domain of West Chester relative to the Norwalk virus potentially result in the formation of these T = 1 capsids.