{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:20:29Z","timestamp":1783405229163,"version":"3.54.6"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>HIV remains globally prevalent, and the long-term complications experienced by people living with HIV (PLWH) have increased interest in the functional heterogeneity of extracellular vesicle (EV) subpopulations. Defining these EV subsets may help clarify HIV-associated immune dysregulation and inform future diagnostic and therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Plasma samples were obtained from three PLWH (HIV\n                      <jats:sup>+<\/jats:sup>\n                      group) and three healthy controls (HC group). Single-EV surface membrane proteins were profiled using the proximity barcoding assay (PBA), and EV subpopulations were identified by FlowSOM clustering with t-SNE visualization. Functional enrichment analysis, protein-protein interaction (PPI) network analysis, and database-based annotation were used to infer putative subpopulation functions and cellular origins. Differentially expressed EV proteins (DEPs) were screened using limma, and ligand-receptor interaction networks were constructed with CellPhoneDB and cross-referenced with publicly available single-cell RNA sequencing data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HIV infection did not appear to alter overall EV abundance but was associated with selective remodeling of EV heterogeneity and expansion of distinct EV subpopulations. CD31\n                      <jats:sup>+<\/jats:sup>\n                      EVs (cluster 2), inferred to be endothelial-derived, were markedly enriched in PLWH. Ligand-receptor analysis suggested that CD31\n                      <jats:sup>+<\/jats:sup>\n                      EVs may communicate with CD16\n                      <jats:sup>+<\/jats:sup>\n                      monocytes through F11R-ITGAL\/ITGB2 and with plasmablasts through CD31-CD38 interactions; these interactions were associated with inflammatory, leukocyte transendothelial migration, and metabolic pathways. In addition, HIV-enriched B2M\n                      <jats:sup>+<\/jats:sup>\n                      EVs (clusters 3) and MUC16\n                      <jats:sup>+<\/jats:sup>\n                      EVs (clusters 9) showed predicted interactions with CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and with CD8\n                      <jats:sup>+<\/jats:sup>\n                      effector memory T and NK cells, respectively, suggesting potential effects on reservoir-related and cytotoxicity-related programs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These exploratory findings suggest that EV heterogeneity may encode cell-type-specific immune regulatory information in HIV infection and highlight CD31\n                      <jats:sup>+<\/jats:sup>\n                      EVs as a candidate EV subset associated with HIV-related immune dysregulation. Larger cohorts and functional validation are required before these EV populations can be considered therapeutic targets for HIV cure strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1871641","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:45:12Z","timestamp":1783403112000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic profiling of single extracellular vesicles reveals association of CD31+ EV subpopulation with immune dysregulation in people living with HIV"],"prefix":"10.3389","volume":"17","author":[{"given":"Ning","family":"Ding","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory for HIV\/AIDS Research, Sino-French Joint Laboratory for HIV\/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University","place":["Beijing, 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