HIV-infection and cocaine use regulate semen extracellular vesicles proteome and miRNAome in a manner that mediates strategic monocyte haptotaxis governed by miR-128 network

Hussein Kaddour, Steven Kopcho, Yuan Lyu, Nadia Shouman, Victor Paromov, Siddharth Pratap, Chandravanu Dash, Eun Young Kim, Jeremy Martinson, Heather McKay, Marta Epeldegui, Joseph B. Margolick, Jack T. Stapleton, Chioma M. Okeoma

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Extracellular vesicles (EVs) are regulators of cell–cell interactions and mediators of horizontal transfer of bioactive molecules between cells. EV-mediated cell–cell interactions play roles in physiological and pathophysiological processes, which maybe modulated by exposure to pathogens and cocaine use. However, the effect of pathogens and cocaine use on EV composition and function are not fully understood. Results: Here, we used systems biology and multi-omics analysis to show that HIV infection (HIV +) and cocaine (COC) use (COC +) promote the release of semen-derived EVs (SEV) with dysregulated extracellular proteome (exProtein), miRNAome (exmiR), and exmiR networks. Integrating SEV proteome and miRNAome revealed a significant decrease in the enrichment of disease-associated, brain-enriched, and HIV-associated miR-128-3p (miR-128) in HIV + COC + SEV with a concomitant increase in miR-128 targets—PEAK1 and RND3/RhoE. Using two-dimensional-substrate single cell haptotaxis, we observed that in the presence of HIV + COC + SEV, contact guidance provided by the extracellular matrix (ECM, collagen type 1) network facilitated far-ranging haptotactic cues that guided monocytes over longer distances. Functionalizing SEV with a miR-128 mimic revealed that the strategic changes in monocyte haptotaxis are in large part the result of SEV-associated miR-128. Conclusions: We propose that compositionally and functionally distinct HIV + COC + and HIV–COC– SEVs and their exmiR networks may provide cells relevant but divergent haptotactic guidance in the absence of chemotactic cues, under both physiological and pathophysiological conditions.

Original languageEnglish (US)
Article number5
JournalCellular and Molecular Life Sciences
Volume79
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • Cocaine
  • Extracellular vesicles
  • Haptotaxis
  • Proteomics
  • Small RNA-Seq
  • miR-128-3p

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Medicine
  • Molecular Biology
  • Cell Biology
  • Pharmacology

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