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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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Notch4 protein is detected in plasma exosome fractions from HIV-positive subjects on ART and correlates with immune activation markers. Plasma exosome fraction (25 μg protein per lane, Ctrl = PBS blank) immunoblotted with Notch4 and exosome marker antibodies (top left). Blots are cropped and full-length blots are included in Supplementary Figure S6. Notch4 protein measured by ELISA in exosome fractions from aviremic and viremic HIV-positive versus HIV-negative subjects (top middle). Horizontal bars represent mean, error bars represent SD. P-values calculated by Mann-Whitney U test. Plasma K:T ratio is increased in aviremic and viremic HIV-positive subjects versus controls (top right). Medians in boxplots are represented by horizontal bars, boxes span the interquartile range (IQR), and whiskers extend to extreme data points within 1.5 times IQR. Outliers are plotted outside 1.5 times IQR. P-values calculated by Welch’s t-test (n = 21 HIV-negative, n = 18 aviremic, and n = 13 viremic HIV-positive subjects). Notch4 levels in HIV-positive plasma exosome fractions correlate negatively with increasing CD4/CD8 ratio and positively with K:T ratio and exosome-HLA-DRA levels in Pearson correlations (bottom panels, p < 0.05; n = 25–27).