巨细胞病毒和 Epstein-Barr 病毒复制对 HIV 感染和未感染个体肠道黏膜基因表达和微生物组组成的影响。
Effect of cytomegalovirus and Epstein-Barr virus replication on intestinal mucosal gene expression and microbiome composition of HIV-infected and uninfected individuals.
机构信息
aDivision of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California bDivision of Gastroenterology, Department of Internal Medicine cDepartment of Immunology-Microbiology, Rush University Medical Center, Chicago, Illinois, USA. *Sara Gianella and Antoine Chaillon contributed equally to the article.
出版信息
AIDS. 2017 Sep 24;31(15):2059-2067. doi: 10.1097/QAD.0000000000001579.
BACKGROUND
HIV-infection is associated with dramatic changes in the intestinal mucosa. The impact of other viral pathogens is unclear.
METHODS
One hundred and eight (108) biopsies from left and right colon (n = 79) and terminal ileum (n = 29) were collected from 19 HIV-infected and 22 HIV-uninfected participants. Levels of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA were measured by droplet digital PCR. Mucosal gene expression was measured via multiplex-assay. Microbiome analysis was performed using bacterial 16S-rDNA-pyrosequencing. The effect of CMV and EBV replication on the microbiome composition and mRNA-expression of selected cytokines (IL-6, IFN-γ, IL-1β, CCL2, IL-8, and IFN-β1) was evaluated.
RESULTS
Overall, CMV and EBV were detected in at least one intestinal site in 60.5 and 78.9% of participants, respectively. HIV-infected individuals demonstrated less detectable CMV (PB = 0.02); CMV was more frequently detected in terminal ileum than colon (PB = 0.05). Detectable EBV was more frequent among HIV-infected (P B= 0.04) without differences by intestinal site. The number of operational taxonomic units did not differ by CMV or EBV detection status. Among HIV-infected participants, higher CMV was only associated with lower relative abundance of Actinobacteria in the ileum (P = 0.03). Presence of CMV was associated with upregulated expression of all selected cytokines in the ileum (all P < 0.02) and higher expression of IL-8 and IFN-β1 in the colon (all P < 0.05) of HIV-uninfected participants, but not among HIV-infected. EBV had no effect on cytokine expression or microbiome composition whatsoever.
CONCLUSION
These results illustrate a complex interplay among HIV-infection, intestinal CMV replication, and mucosal gut environment, and highlight a possible modulatory effect of CMV on the microbial and immune homeostasis.
背景
HIV 感染会导致肠道黏膜发生显著变化。其他病毒病原体的影响尚不清楚。
方法
从 19 名 HIV 感染和 22 名 HIV 未感染的参与者的左、右结肠（n=79）和末端回肠（n=29）中采集了 108 个活检样本。通过液滴数字 PCR 测量巨细胞病毒（CMV）和 Epstein-Barr 病毒（EBV）DNA 的水平。通过多重分析测量黏膜基因表达。使用细菌 16S-rDNA 焦磷酸测序进行微生物组分析。评估 CMV 和 EBV 复制对微生物组组成和选定细胞因子（IL-6、IFN-γ、IL-1β、CCL2、IL-8 和 IFN-β1）mRNA 表达的影响。
结果
总体而言，CMV 和 EBV 分别在 60.5%和 78.9%的参与者的至少一个肠道部位被检测到。HIV 感染者的 CMV 检测率较低（PB=0.02）；CMV 在回肠中比结肠中更常被检测到（PB=0.05）。在 HIV 感染者中，可检测到 EBV 的频率更高（P<0.04），但与肠道部位无关。CMV 或 EBV 检测状态与可操作分类单位的数量无差异。在 HIV 感染者中，CMV 水平较高仅与回肠中放线菌的相对丰度较低相关（P=0.03）。CMV 的存在与回肠中所有选定细胞因子的表达上调（均 P<0.02）以及 HIV 未感染者结肠中 IL-8 和 IFN-β1 表达升高（均 P<0.05）相关，但在 HIV 感染者中则无相关性。EBV 对细胞因子表达或微生物组组成没有任何影响。
结论
这些结果说明了 HIV 感染、肠道 CMV 复制和黏膜肠道环境之间的复杂相互作用，并强调了 CMV 对微生物和免疫稳态可能具有调节作用。
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