Department of Biology, University Park, USA.
Center for Infectious Disease Dynamics, Huck Institutes of the Life Sciences, USA.
J Gen Virol. 2022 Oct;103(10). doi: 10.1099/jgv.0.001780.
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 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.
单纯疱疹病毒 1（HSV1）最常引起口腔病变和轻微的临床症状，但它也可导致多种严重程度和复发率的疾病。为了更好地理解这种表型变异，我们对来自具有不同感染结局的个体的 11 株 HSV1 进行了分离和鉴定。我们提供了这些分离株的基因组和蚀斑表型分析的新数据，并将这些数据与之前在小鼠动物模型中对每种菌株疾病表型的定量报告进行了比较。我们发现，将这三种类型的数据相结合，可以将这些 HSV1 菌株聚类为四个组，而不能仅通过任何单一数据集来区分，这突出了组合多参数表型分析的优势。两种菌株（第 1 组）产生部分或完全合胞体蚀斑表型，并在小鼠中导致疾病表型减弱。三种中等大小蚀斑的菌株，在小鼠中引起严重疾病，遗传聚类为第二组（第 2 组）。六个平均蚀斑尺寸最小的菌株根据其在小鼠中的不同遗传聚类和疾病严重程度分为两个亚组（第 3 组和第 4 组）。比较基因组学和网络图分析表明，具有减弱与毒力表型的 HSV1 分离株存在分离。这些观察结果表明，这些菌株的毒力表型可能与 HSV1 群体内的遗传变异有关。
