Human microbiome studies have revealed the intricate interplay of host immunity and bacterial communities to achieve homeostatic balance. Healthy skin microbial communities are dominated by bacteria with low viral representation^1-3, mainly bacteriophage. Specific eukaryotic viruses have been implicated in both common and rare skin diseases, but cataloging skin viral communities has been limited. Alterations in host immunity provide an opportunity to expand our understanding of microbial-host interactions. Primary immunodeficient patients manifest with various viral, bacterial, fungal, and parasitic infections, including skin infections⁴. Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility⁵. DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen-dense tissues such as skin⁶. Analyzing deep metagenomic sequencing data from DOCK8-deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity compared with healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8-deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.

中文翻译：

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DOCK8 缺陷患者的皮肤病毒组扩大。

人类微生物组研究揭示了宿主免疫和细菌群落之间复杂的相互作用以实现稳态平衡。健康皮肤微生物群落以病毒代表性较低的细菌为主^1-3，主要是噬菌体。特定的真核病毒与常见和罕见的皮肤病有关，但对皮肤病毒群落的分类仍然有限。宿主免疫力的改变为扩大我们对微生物与宿主相互作用的理解提供了机会。原发性免疫缺陷患者表现为各种病毒、细菌、真菌和寄生虫感染，包括皮肤感染⁴。胞质分裂专用者 8 (DOCK8) 缺陷是一种罕见的原发性人类免疫缺陷，其特征是反复皮肤和全身感染，以及特应性和癌症易感性⁵。DOCK8 编码在淋巴细胞中高度表达的鸟嘌呤核苷酸交换因子，可调节肌动蛋白细胞骨架，这对于穿过皮肤等胶原蛋白密集组织的迁移至关重要⁶。分析 DOCK8 缺陷皮肤样本的深度宏基因组测序数据表明，与健康志愿者相比，真核病毒的代表性和多样性显着增加。从头组装方法鉴定了数百个新型人乳头瘤病毒基因组，阐明了微生物暗物质。DOCK8 缺陷患者皮肤病毒组的扩展强调了免疫监视在控制真核病毒定植和感染中的重要性。