Journal
AIDS
Volume 31, Issue 15, Pages 2059-2067Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000001579
Keywords
cytomegalovirus and Epstein-Barr virus replication; HIV infection; intestinal microbiome; mucosal cytokine expression
Categories
Funding
- National Institutes of Health [AI100665, MH100974, MH097520, DA034978, AI007384, AI027763, AI106039, AI43638, AI074621, AI036214, MH101012, UL1TR000100, CARE U19 AI096113, AI068636-09]
- University of California
- San Francisco-Gladstone Institute of Virology & Immunology Center for AIDS Research [P30-AI027763]
- California HIV Research Program Ideal award
- department of Veterans Affairs
- James B. Pendleton Charitable Trust
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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-gamma, IL-1 beta, CCL2, IL-8, and IFN-beta 1) 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 (P = 0.04); CMV was more frequently detected in terminal ileum than colon (P = 0.04). Detectable EBV was more frequent among HIV-infected (P = 0.05) 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-b1 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. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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