Comparison of Herpes Simplex Virus 1 Strains Circulating in Finland Demonstrates the Uncoupling of Whole-Genome Relatedness and Phenotypic Outcomes of Viral Infection
Comparison of Herpes Simplex Virus 1 Strains Circulating in Finland Demonstrates the Uncoupling of Whole-Genome Relatedness and Phenotypic Outcomes of Viral Infection
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DOI：
10.1128/jvi.01824-18
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发表时间：
2019-04-01
影响因子：
5.4
通讯作者：
Szpara, Moriah L.
中科院分区：
文献类型：
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作者：
Bowen, Christopher D.;Paavilainen, Henrik;Szpara, Moriah L.
芬兰的大多数成年人是单纯疱疹病毒（HSV）血清阳性携带者。感染发生在上皮或粘膜表面，之后病毒体进入支配神经末梢，最终在感觉或自主神经系统的神经元中建立终身感染。最近的数据突出了HSV-1菌株的遗传多样性，并证明了菌株相似性的明显地理模式。尽管迄今为止欧洲已经对多个HSV-1基因组进行了测序，但缺乏来自北欧国家的测序基因组。芬兰历史上至少有两次大规模的人口迁移，这表明各种病毒可能在人口中持续存在。在这里，我们使用来自芬兰的HSV-1临床分离株来测试病毒发生、遗传变异和表型特征之间的关系。我们发现芬兰HSV-1分离株分为两个不同的系统发育组，可能反映了人类（和病毒）迁移到芬兰的历史浪潮。每种HSV-1分离株在细胞培养中具有一组不同的表型，包括病毒产生量、细胞外病毒释放和细胞类型特异性适应性的差异。重要的是，系统发生簇不能预测表型差异中的任何可检测模式，表明全基因组相关性不是总体病毒表型的代表。相反，我们强调了可能导致观察到的表型差异的特定基因水平差异，并且我们注意到来自不同系统发育组的菌株可能包含相同的遗传变异。重要信息单纯疱疹病毒（HSV）感染大多数成年人。最近的数据突出了HSV-1菌株的遗传多样性，并证明了来自相同地理区域的菌株之间存在明显的基因组相关性。我们使用来自芬兰的HSV-1临床分离株来测试病毒基因组和地理关系之间的关系，特定基因的差异和病毒感染的特征。我们发现，来自芬兰的病毒分离株分为两组不同的基因组和地理相关性，可能反映了人类和病毒迁移到芬兰的历史模式。这些芬兰HSV-1分离株在检测的多种细胞类型中具有不同的感染特征，这些特征对每种分离株都具有特异性，并且不根据基因组和地理相关性进行分组。这表明，HSV-1株感染的具体特征的差异是由宿主细胞类型和特定病毒基因水平差异的组合决定的。
A majority of adults in Finland are seropositive carriers of herpes simplex viruses (HSV). Infection occurs at epithelial or mucosal surfaces, after which virions enter innervating nerve endings, eventually establishing lifelong infection in neurons of the sensory or autonomic nervous system. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent geographic patterns in strain similarity. Though multiple HSV-1 genomes have been sequenced from Europe to date, there is a lack of sequenced genomes from the Nordic countries. Finland's history includes at least two major waves of human migration, suggesting the potential for diverse viruses to persist in the population. Here, we used HSV-1 clinical isolates from Finland to test the relationship between viral phylogeny, genetic variation, and phenotypic characteristics. We found that Finnish HSV-1 isolates separated into two distinct phylogenetic groups, potentially reflecting historical waves of human (and viral) migration into Finland. Each HSV-1 isolate harbored a distinct set of phenotypes in cell culture, including differences in the amount of virus production, extracellular virus release, and cell-type-specific fitness. Importantly, the phylogenetic clusters were not predictive of any detectable pattern in phenotypic differences, demonstrating that whole-genome relatedness is not a proxy for overall viral phenotype. Instead, we highlight specific gene-level differences that may contribute to observed phenotypic differences, and we note that strains from different phylogenetic groups can contain the same genetic variations.IMPORTANCE Herpes simplex viruses (HSV) infect a majority of adults. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent genomic relatedness between strains from the same geographic regions. We used HSV-1 clinical isolates from Finland to test the relationship between viral genomic and geographic relationships, differences in specific genes, and characteristics of viral infection. We found that viral isolates from Finland separated into two distinct groups of genomic and geographic relatedness, potentially reflecting historical patterns of human and viral migration into Finland. These Finnish HSV-1 isolates had distinct infection characteristics in multiple cell types tested, which were specific to each isolate and did not group according to genomic and geographic relatedness. This demonstrates that HSV-1 strain differences in specific characteristics of infection are set by a combination of host cell type and specific viral gene-level differences.