Abstract Herpes Simplex Virus type 1 (HSV-1) chronically infects over 70 per cent of the global population. Clinical manifestations are largely restricted to recurrent epidermal vesicles. However, HSV-1 also leads to encephalitis, the infection of the brain parenchyma, with high associated rates of mortality and morbidity. In this study, we performed target enrichment followed by direct sequencing of HSV-1 genomes, using target enrichment methods on the cerebrospinal fluid (CSF) of clinical encephalitis patients and from skin swabs of epidermal vesicles on non-encephalopathic patients. Phylogenetic analysis revealed high inter-host diversity and little population structure. In contrast, samples from different lesions in the same patient clustered with similar patterns of allelic variants. Comparison of consensus genome sequences shows HSV-1 has been freely recombining, except for distinct islands of linkage disequilibrium (LD). This suggests functional constraints prevent recombination between certain genes, notably those encoding pairs of interacting proteins. Distinct LD patterns characterised subsets of viruses recovered from CSF and skin lesions, which may reflect different evolutionary constraints in different body compartments. Functions of genes under differential constraint related to immunity or tropism and provide new hypotheses on tissue-specific mechanisms of viral infection and latency.

中文翻译：

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直接从人脑脊液中对单纯疱疹病毒 1 进行全基因组测序揭示了嗜神经病毒的选择性限制


摘要 1 型单纯疱疹病毒 (HSV-1) 长期感染全球 70% 以上的人口。临床表现主要限于复发性表皮小泡。然而，HSV-1 也会导致脑炎（脑实质感染），并导致较高的死亡率和发病率。在本研究中，我们对临床脑炎患者的脑脊液 (CSF) 和非脑病患者的表皮囊泡皮肤拭子使用靶点富集方法，进行靶点富集，然后直接对 HSV-1 基因组进行测序。系统发育分析揭示了宿主间的高度多样性和很少的种群结构。相比之下，来自同一患者不同病变的样本聚集了相似的等位基因变异模式。共有基因组序列的比较显示，除了明显的连锁不平衡（LD）岛外，HSV-1 已经自由重组。这表明功能限制阻止了某些基因之间的重组，特别是那些编码相互作用蛋白质对的基因。不同的 LD 模式表征了从脑脊液和皮肤损伤中恢复的病毒子集，这可能反映了不同身体部位的不同进化限制。差异约束下基因的功能与免疫或向性相关，并为病毒感染和潜伏的组织特异性机制提供新的假设。