Multi-phenotype analysis for enhanced classification of 11 herpes simplex virus 1 strains.
Multi-phenotype analysis for enhanced classification of 11 herpes simplex virus 1 strains.
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DOI：
10.1099/jgv.0.001780
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发表时间：
2022-10
影响因子：
3.8
通讯作者：
Szpara, Moriah L
中科院分区：
文献类型：
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作者：
Dweikat, Sarah N;Renner, Daniel W;Bowen, Christopher D;Szpara, Moriah L
单纯疱疹病毒 1 (HSV1) 因引起口腔病变和轻微的临床症状而闻名，但它也能导致多种疾病严重程度和再激活率。为了更好地了解这种表型变异，我们对从具有不同感染结果的个体中分离出的 11 种 HSV1 毒株进行了特征分析。我们提供了这些分离株的基因组和体外噬菌斑表型分析的新数据，并将这些数据与先前报道的小鼠动物模型中每种菌株疾病表型的定量进行比较。我们表明，这三种类型的数据的整合允许将这些 HSV1 毒株聚类成四组，仅靠任何单个数据集都无法区分这些组，这凸显了组合多参数表型分析的好处。两种菌株（第 1 组）在小鼠中产生部分或大部分合胞斑表型并减弱疾病表型。三个中等斑块大小的菌株在小鼠中引起严重疾病，在遗传上聚集到第二组（组2）。根据小鼠中不同的遗传聚类和疾病严重程度，将平均斑块尺寸最小的六种菌株分为两个亚组（第 3 组和第 4 组）。比较基因组学和网络图分析表明，具有减毒表型和强毒表型的 HSV1 分离株是分开的。这些观察结果表明这些毒株的毒力表型可能可追溯到 HSV1 群体内的遗传变异。
Herpes simplex virus 1 (HSV1) is best known for causing oral lesions and mild clinical symptoms, but it can produce a significant range of disease severities and rates of reactivation. To better understand this phenotypic variation, we characterized 11 HSV1 strains that were isolated from individuals with diverse infection outcomes. We provide new data on genomic and in vitro plaque phenotype analysis for these isolates and compare these data to previously reported quantitation of the disease phenotype of each strain in a murine animal model. We show that integration of these three types of data permitted clustering of these HSV1 strains into four groups that were not distinguishable by any single dataset alone, highlighting the benefits of combinatorial multi-parameter phenotyping. Two strains (group 1) produced a partially or largely syncytial plaque phenotype and attenuated disease phenotypes in mice. Three strains of intermediate plaque size, causing severe disease in mice, were genetically clustered to a second group (group 2). Six strains with the smallest average plaque sizes were separated into two subgroups (groups 3 and 4) based on their different genetic clustering and disease severity in mice. Comparative genomics and network graph analysis suggested a separation of HSV1 isolates with attenuated vs. virulent phenotypes. These observations imply that virulence phenotypes of these strains may be traceable to genetic variation within the HSV1 population.