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. 2018 May 8;8:7227. doi: 10.1038/s41598-018-25515-4

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Exosome markers correlate positively with oxidative stress-related metabolites and negatively with levels of n-3 and n-6 polyunsaturated fatty acids. (a) Heatmap shows unsupervised hierarchical clustering of metabolites (n = 16) associated with oxidative stress, tryptophan catabolism, and polyunsaturated fatty acid (PUFA) metabolism that distinguish HIV-positive from HIV-negative control subjects (FC > 1.3, p < 0.05, FDR < 0.10). (b) Metabolites associated with oxidative stress are increased, and the indicated PUFA are decreased in aviremic and viremic HIV-positive subjects versus controls (*p < 0.01, **p < 0.001). Medians represented by horizontal bars, boxes span the IQR, and whiskers extend to extreme data points within 1.5 times IQR. Outliers are plotted outside 1.5 times the IQR. P-values calculated by Welch’s t-test (p < 0.05; n = 26 HIV-negative, n = 21 HIV-positive aviremic, n = 16 HIV-positive viremic subjects). (c) Pearson correlation matrix r-values show positive correlation of exosome marker proteins (CD9 and CD63) with metabolites associated with oxidative stress, and negative correlation with n-3 and n-6 PUFA (p < 0.05). (d) Correlation scatter plots are shown with correlation coefficients and p-values above each plot. n = 36 HIV-positive, 26 HIV-negative. EPA, eicosapentaenoate (20:5n3); DHA, docosahexaenoate (22:6n3); n3 DPA, docosapentaenoate (22:5n3); n6 DPA, docosapentaenoate (22:5n6); K:T ratio, kynurenine: tryptophan ratio. Scatter plots showing Pearson correlation plots for additional exosome markers and metabolites are in Supplementary Figure S4.