Effect of cytomegalovirus and Epstein-Barr virus replication on intestinal mucosal gene expression and microbiome composition of HIV-infected and uninfected individuals. Gianella, S., Chaillon, A., Mutlu, E. A., Engen, P. A., Voigt, R. M., Keshavarzian, A., Losurdo, J., Chakradeo, P., Lada, S. M., Nakazawa, M., & Landay, A. L. AIDS (London, England), 31(15):2059–2067, 2017.
doi  abstract   bibtex   
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 (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-β1 in the colon (all P \textless 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.
@article{gianella_effect_2017,
	title = {Effect of cytomegalovirus and {Epstein}-{Barr} virus replication on intestinal mucosal gene expression and microbiome composition of {HIV}-infected and uninfected individuals},
	volume = {31},
	issn = {1473-5571},
	doi = {10.1097/QAD.0000000000001579},
	abstract = {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 (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-β1 in the colon (all P {\textless} 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.},
	language = {eng},
	number = {15},
	journal = {AIDS (London, England)},
	author = {Gianella, Sara and Chaillon, Antoine and Mutlu, Ece A. and Engen, Phillip A. and Voigt, Robin M. and Keshavarzian, Ali and Losurdo, John and Chakradeo, Prachi and Lada, Steven M. and Nakazawa, Masato and Landay, Alan L.},
	year = {2017},
	pmid = {28906277},
	pmcid = {PMC5654609},
	keywords = {Biopsy, Colon, Cytokines, Cytomegalovirus Infections, DNA, Bacterial, DNA, Ribosomal, DNA, Viral, Epstein-Barr Virus Infections, Female, Gastrointestinal Microbiome, Gene Expression Profiling, Gene Expression Regulation, HIV Infections, Humans, Ileum, Intestinal Mucosa, Male, Microbiota, Middle Aged, Polymerase Chain Reaction, RNA, Ribosomal, 16S, Sequence Analysis, DNA, Viral Load},
	pages = {2059--2067},
}

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