Abstract：
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.
摘要：
单纯疱疹病毒1型（HSV1）以引起口腔病变和轻度临床症状而闻名，但是它可以产生很大范围的疾病严重程度和再激活率。为了更好地理解这种表型变异，我们对从感染结局不同的个体中分离出的11株HSV1菌株进行了鉴定.我们提供了有关这些分离株的基因组和体外空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的疾病表型的定量进行了比较。我们表明，整合这三种类型的数据允许将这些HSV1菌株聚类成四个组，这些组仅通过任何单个数据集无法区分。强调组合多参数表型的好处。两个菌株(组1)在小鼠中产生部分或大部分合胞菌斑表型和减弱的疾病表型。三株中间菌斑大小，在小鼠中引起严重的疾病，被遗传聚类到第二组(第2组)。根据小鼠中不同的遗传聚类和疾病严重程度，将具有最小平均斑块大小的六个菌株分为两个亚组（组3和4）。比较基因组学和网络图分析表明，分离出具有减毒与减毒的HSV1分离株。毒力表型。这些观察结果表明，这些菌株的毒力表型可能可追溯到HSV1种群内的遗传变异。
