Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 1088639, Japan.
Department of Pathology, National Institute of Infectious Diseases, Tokyo, 1628640, Japan.
BMC Biol. 2020 Jun 4;18(1):55. doi: 10.1186/s12915-020-00785-5.
Human-resident microbes can influence both health and disease. Investigating the microbiome using next-generation sequencing technology has revealed examples of mutualism and conflict between microbes and humans. Comparing to bacteria, the viral component of the microbiome (i.e., the "virome") is understudied. Somatic tissues of healthy individuals are usually inaccessible for the virome sampling; therefore, there is limited understanding of the presence and distribution of viruses in tissues in healthy individuals and how virus infection associates with human gene expression and perturbs immunological homeostasis.
To characterize the human virome in a tissue-specific manner, here we performed meta-transcriptomic analysis using the RNA-sequencing dataset from the Genotype-Tissue Expression (GTEx) Project. We analyzed the 8991 RNA-sequencing data obtained from 51 somatic tissues from 547 individuals and successfully detected 39 viral species in at least one tissue. We then investigated associations between virus infection and human gene expression and human disease onset. We detected some expected relationships; for instance, hepatitis C virus infection in the liver was strongly associated with interferon-stimulated gene upregulation and pathological findings of chronic hepatitis. The presence of herpes simplex virus type 1 in one subject's brain strongly associated with immune gene expression. While torque teno virus was detected in a broad range of human tissues, it was not associated with interferon responses. Being notable in light of its association with lymphoproliferative disorders, Epstein-Barr virus infection in the spleen and blood was associated with an increase in plasma cells in healthy subjects. Human herpesvirus 7 was often detected in the stomach; intriguingly, it associated with the proportion of human leukocytes in the stomach as well as digestive gene expression. Moreover, virus infections in the local tissues associated with systemic immune responses in circulating blood.
To our knowledge, this study is the first comprehensive investigation of the human virome in a variety of tissues in healthy individuals through meta-transcriptomic analysis. Further investigation of the associations described here, and application of this analytical pipeline to additional datasets, will be useful to reveal the impact of viral infections on human health.
人类常驻微生物既能影响健康，也能引发疾病。利用下一代测序技术研究微生物组，揭示了微生物与人类之间存在共生和冲突的例子。与细菌相比，微生物组的病毒成分（即“病毒组”）研究较少。健康个体的体组织通常无法用于病毒组采样；因此，人们对健康个体组织中病毒的存在和分布，以及病毒感染如何与人类基因表达相关联并扰乱免疫稳态知之甚少。
为了以组织特异性的方式描述人类病毒组，我们在这里使用基因型-组织表达（GTEx）项目的 RNA 测序数据集进行了元转录组分析。我们分析了从 547 名个体的 51 个体组织中获得的 8991 个 RNA 测序数据，并成功地在至少一种组织中检测到 39 种病毒。然后，我们研究了病毒感染与人类基因表达和人类疾病发病之间的关联。我们检测到了一些预期的关系；例如，肝脏中的丙型肝炎病毒感染与干扰素刺激基因的上调和慢性肝炎的病理发现密切相关。一位受试者大脑中单纯疱疹病毒 1 的存在与免疫基因表达强烈相关。虽然乳头多瘤空泡病毒在广泛的人类组织中被检测到，但它与干扰素反应无关。值得注意的是，EB 病毒在脾脏和血液中的感染与健康受试者血浆细胞的增加有关。人疱疹病毒 7 常被检测到在胃中；有趣的是，它与胃中的人类白细胞比例以及消化基因表达有关。此外，局部组织中的病毒感染与循环血液中的全身免疫反应有关。
据我们所知，这是通过元转录组分析首次对健康个体多种组织中的人类病毒组进行的全面研究。进一步研究这里描述的关联，并将这种分析方法应用于其他数据集，将有助于揭示病毒感染对人类健康的影响。
