The human skin double-stranded DNA virome: topographical and temporal diversity, genetic enrichment, and dynamic associations with the host microbiome.
The human skin double-stranded DNA virome: topographical and temporal diversity, genetic enrichment, and dynamic associations with the host microbiome.
复制标题
人皮肤双链DNA病毒素：地形和时间多样性，遗传富集以及与宿主微生物组的动态关联。
DOI：
10.1128/mbio.01578-15
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发表时间：
2015-10-20
期刊：
影响因子：
6.4
通讯作者：
Grice EA
中科院分区：
文献类型：
--
作者：
Hannigan GD;Meisel JS;Tyldsley AS;Zheng Q;Hodkinson BP;SanMiguel AJ;Minot S;Bushman FD;Grice EA
病毒是人类微生物群的主要组成部分，但在皮肤（我们抵御外部环境的主要屏障）中人们对病毒知之甚少。病毒群落具有调节皮肤健康和疾病状态的潜力。已知噬菌体通过捕食和遗传交换影响微生物群落的结构和功能。人类病毒与皮肤癌和多种皮肤表现有关。尽管有这些重要作用，但人们对人类皮肤病毒组及其与宿主微生物组的相互作用知之甚少。在这里，我们通过对纯化的病毒样颗粒 (VLP) 的 DNA 进行宏基因组测序来评估人皮肤双链 DNA 病毒组。与此同时，我们采用了整个皮肤微生物组的宏基因组测序来评估共变并推断与病毒组的相互作用。样本是在 1 个月内从 16 名受试者的 8 个身体部位采集的。除了已知分隔细菌和真菌微生物群的微环境之外，自然皮肤闭塞与皮肤病毒群落组成密切相关。病毒重叠群富集了指示温带噬菌体复制风格的基因，并且还保留了编码潜在抗生素抗性和毒力因子的基因。在细菌 DNA 序列中鉴定出的 CRISPR 间隔区提供了噬菌体捕食的记录，并提出了一种解释皮肤噬菌体群落空间划分的机制。最后，我们对细菌和噬菌体群落的结构进行了建模，以揭示具有棒状杆菌中心的复杂微生物环境。这些结果揭示了之前未被充分认识的人类皮肤病毒组的多样性、编码功能和病毒-微生物动态。迄今为止，大多数皮肤微生物组研究都集中在细菌和真菌群落上。尽管皮肤病毒群落及其与宿主的关系具有调节皮肤健康和疾病状态的潜力，但人们对它们的了解仍然知之甚少。先前的研究采用未纯化的病毒样颗粒（VLP）的全宏基因组测序，提供了对皮肤微生物组的病毒成分的一些见解，但尚未完全表征这些群落或分析与宿主微生物组的相互作用。在这里，我们提出了一种优化的病毒纯化技术和相应的分析工具，以获得对皮肤病毒组的新见解，包括病毒“暗物质”及其与宿主微生物组的潜在相互作用。这里介绍的工作建立了健康人类皮肤病毒组的基线，并且是未来研究检查皮肤健康和疾病中病毒扰动的必要基础。
Viruses make up a major component of the human microbiota but are poorly understood in the skin, our primary barrier to the external environment. Viral communities have the potential to modulate states of cutaneous health and disease. Bacteriophages are known to influence the structure and function of microbial communities through predation and genetic exchange. Human viruses are associated with skin cancers and a multitude of cutaneous manifestations. Despite these important roles, little is known regarding the human skin virome and its interactions with the host microbiome. Here we evaluated the human cutaneous double-stranded DNA virome by metagenomic sequencing of DNA from purified virus-like particles (VLPs). In parallel, we employed metagenomic sequencing of the total skin microbiome to assess covariation and infer interactions with the virome. Samples were collected from 16 subjects at eight body sites over 1 month. In addition to the microenviroment, which is known to partition the bacterial and fungal microbiota, natural skin occlusion was strongly associated with skin virome community composition. Viral contigs were enriched for genes indicative of a temperate phage replication style and also maintained genes encoding potential antibiotic resistance and virulence factors. CRISPR spacers identified in the bacterial DNA sequences provided a record of phage predation and suggest a mechanism to explain spatial partitioning of skin phage communities. Finally, we modeled the structure of bacterial and phage communities together to reveal a complex microbial environment with a Corynebacterium hub. These results reveal the previously underappreciated diversity, encoded functions, and viral-microbial dynamic unique to the human skin virome. To date, most cutaneous microbiome studies have focused on bacterial and fungal communities. Skin viral communities and their relationships with their hosts remain poorly understood despite their potential to modulate states of cutaneous health and disease. Previous studies employing whole-metagenome sequencing without purification for virus-like particles (VLPs) have provided some insight into the viral component of the skin microbiome but have not completely characterized these communities or analyzed interactions with the host microbiome. Here we present an optimized virus purification technique and corresponding analysis tools for gaining novel insights into the skin virome, including viral “dark matter,” and its potential interactions with the host microbiome. The work presented here establishes a baseline of the healthy human skin virome and is a necessary foundation for future studies examining viral perturbations in skin health and disease.