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.
AIDS. 2017 Sep 24;31(15):2059-2067. doi: 10.1097/QAD.0000000000001579.
HIV-infection is associated with dramatic changes in the intestinal mucosa. The impact of other viral pathogens is unclear.
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.
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.
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.
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。
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。
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。
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。
