Genetic and phenotypic intrastrain variation in herpes simplex virus type 1 Glasgow strain 17 syn+-derived viruses
Genetic and phenotypic intrastrain variation in herpes simplex virus type 1 Glasgow strain 17 syn+-derived viruses
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DOI：
10.1099/jgv.0.001343
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发表时间：
2019-01-01
影响因子：
3.8
通讯作者：
Elliott, Gillian
中科院分区：
文献类型：
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作者：
Jones, Juliet;Depledge, Daniel Pearce;Elliott, Gillian
单纯疱疹病毒1型（HSV 1）的格拉斯哥s17 syn+毒株可以说是最好的特征毒株，并为HSV 1遗传研究提供了参考序列。在这里，我们表明，我们最初的s17 syn+股票是一个混合的人口，我们已经分离出一个小的变种，不像其他菌株在实验室中，未能有效地从感染的细胞释放和传播主要是通过直接细胞到细胞的传输。对其他地方分离的其他s17衍生病毒的分析显示，许多病毒具有相同的释放表型。第二代测序的8个空斑纯化的s17衍生的病毒揭示了50个单核苷酸多态性（SNPs），包括约10个编码SNPs不同的序列。这与Sc16菌株中约800个SNP的菌株间变异相比，其中四分之一是编码变化。在s17中发现的变异中，我们在病毒的原始原种中鉴定了13种糖蛋白C的变异体，这些变异体主要是C残基的均聚物改变的结果。对编码不同形式gC的七个分离株的表征表明，尽管其中六个分离株缺乏跨膜结构域，但所有分离株均得到表达。虽然释放表型与这些鉴定的gC变异中的任何一种都不直接相关，但进一步证明了HSV 1的9个临床分离株也未能通过细胞外释放传播，这提高了组织培养中的繁殖改变了HSV 1 s17传播表型的可能性。因此，这里确定的s17株内变异为理解HSV 1传播和组织培养适应提供了一个很好的模型。
The Glasgow s17 syn+ strain of herpes simplex virus 1 (HSV1) is arguably the best characterized strain and has provided the reference sequence for HSV1 genetic studies. Here we show that our original s17 syn+ stock was a mixed population from which we have isolated a minor variant that, unlike other strains in the laboratory, fails to be efficiently released from infected cells and spreads predominantly by direct cell-to-cell transmission. Analysis of other s17-derived viruses that had been isolated elsewhere revealed a number with the same release phenotype. Second-generation sequencing of 8 plaque-purified s17-derived viruses revealed sequences that vary by 50 single-nucleotide polymorphisms (SNPs), including approximately 10 coding SNPs. This compared to interstrain variations of around 800 SNPs in strain Sc16, of which a quarter were coding changes. Amongst the variations found within s17, we identified 13 variants of glycoprotein C within the original stock of virus that were predominantly a consequence of altered homopolymeric runs of C residues. Characterization of seven isolates coding for different forms of gC indicated that all were expressed, despite six of them lacking a transmembrane domain. While the release phenotype did not correlate directly with any of these identified gC variations, further demonstration that nine clinical isolates of HSV1 also fail to spread through extracellular release raises the possibility that propagation in tissue culture had altered the HSV1 s17 transmission phenotype. Hence, the s17 intrastrain variation identified here offers an excellent model for understanding both HSV1 transmission and tissue culture adaption.