title: Elevated Abundance, Size, and MicroRNA Content of Plasma Extracellular Vesicles in Viremic HIV-1+ Patients: Correlations With Known Markers of Disease Progression.
abstract: BACKGROUND
  Because of factors only partly understood, the generalized elevated immune activation and inflammation characterizing HIV-1-infected patients are corrected incompletely with antiretroviral therapy (ART). Extracellular vesicles (EVs) including exosomes and microvesicles released by several cell types may contribute to immune activation and dysfunction. EV size, abundance, and content appear to differ according to infection phase, disease progression, and ART.
  
  
  METHODS
  We examined whether the size of EVs and the abundance of exosomes in plasma are associated with cell and tissue activation as well as with viral production. Acetylcholinesterase-bearing (AChE+) exosomes in plasma were quantified using an AChE assay. EV size was analyzed using dynamic light scattering. Proteins and microRNAs present in EVs were detected by Western blot and real-time polymerase chain reaction, respectively.
  
  
  RESULTS
  Exosomes were found more abundant in the plasma of ART-naive patients. EV size was larger in ART-naive than in ART-suppressed patients, elite controllers, or healthy control subjects. Both exosome abundance and EV sizes were inversely correlated with CD4/CD8 T-cell ratio and neutrophil, platelet, and CD4 T-cell counts and positively correlated with CD8 T-cell counts. A negative correlation was found between CD4 T-cell nadir and exosome abundance, but not EV size. Levels of miR-155 and miR-223 but not miR-92 were strongly correlated negatively with EV abundance and size in ART-naive patients.
  
  
  CONCLUSIONS
  Monitoring of circulating EVs and EV-borne microRNA is possible and may provide new insight into HIV-1 pathogenesis, disease progression, and the associated inflammatory state, as well as the efficacy of ART and the treatments intended to reduce immune activation.
authors.affiliation: *Centre de recherche du CHU de Québec and Faculty of Medicine, Département de microbiologie infectiologie et immunologie, Université Laval, Québec, Québec, Canada; †Département des Sciences Biologiques et Centre de recherche BioMed, Université du Québec à Montréal (UQAM), Montréal, Québec, Canada; ‡Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Département de microbiologie infectiologie et immunologie, Montréal, Québec, Canada; and §Chronic Viral Illness Service and Research Institute, McGill University Health Centre, Montréal, Québec, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Hubert
authors.forename: Caroline
authors.initials: C
authors.lastname: Subra
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Tremblay Labrecque
authors.forename: Cécile
authors.initials: C
authors.lastname: Tremblay
authors.forename: Benoit
authors.initials: B
authors.lastname: Laffont
authors.forename: Patrick
authors.initials: P
authors.lastname: Provost
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Caroline
authors.initials: C
authors.lastname: Gilbert
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015415:Biomarkers; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D055354:Exosomes / Q000502:physiology; D000067128:Extracellular Vesicles / Q000737:chemistry* / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D035683:MicroRNAs