Hussein Kaddour1,2, Steven Kopcho1, Yuan Lyu1, Nadia Shouman1, Victor Paromov3, Siddharth Pratap4, Chandravanu Dash5, Eun-Young Kim6, Jeremy Martinson7, Heather McKay8, Marta Epeldegui9,10,11, Joseph B Margolick12, Jack T Stapleton13, Chioma M Okeoma14. 1. Department of Pharmacology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, 11794-8651, USA. 2. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 10591, USA. 3. CRISALIS, School of Graduate Studies and Research, Proteomics Core, Meharry Medical College, Nashville, TN, 37208, USA. 4. CRISALIS, School of Graduate Studies and Research, Bioinformatics Core, Meharry Medical College, Nashville, TN, 37208, USA. 5. Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN, 37208, USA. 6. Division of Infectious Diseases, Department of Medicine, Northwestern University, Chicago, IL, 60611, USA. 7. Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA. 8. Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. 9. Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, UCLA AIDS Institute and UCLA Jonsson Comprehensive Cancer Center, Los Angeles, USA. 10. David Geffen School of Medicine at UCLA, UCLA AIDS Institute, Los Angeles, USA. 11. UCLA Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, USA. 12. Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21207, USA. 13. Departments of Internal Medicine, Microbiology and Immunology, University of Iowa and Iowa City Veterans Administration Healthcare, Iowa City, IA, 52242-1081, USA. 14. Department of Pharmacology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, 11794-8651, USA. chioma.okeoma@stonybrook.edu.
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.
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.
Authors: E Dulioust; A Le Du; D Costagliola; J Guibert; J-M Kunstmann; I Heard; J-C Juillard; D Salmon; M Leruez-Ville; L Mandelbrot; C Rouzioux; D Sicard; J-R Zorn; P Jouannet; M De Almeida Journal: Hum Reprod Date: 2002-08 Impact factor: 6.918
Authors: Ioannis S Vlachos; Konstantinos Zagganas; Maria D Paraskevopoulou; Georgios Georgakilas; Dimitra Karagkouni; Thanasis Vergoulis; Theodore Dalamagas; Artemis G Hatzigeorgiou Journal: Nucleic Acids Res Date: 2015-05-14 Impact factor: 16.971
Authors: Jennifer C Chan; Christopher P Morgan; N Adrian Leu; Amol Shetty; Yasmine M Cisse; Bridget M Nugent; Kathleen E Morrison; Eldin Jašarević; Weiliang Huang; Nickole Kanyuch; Ali B Rodgers; Natarajan V Bhanu; Dara S Berger; Benjamin A Garcia; Seth Ament; Maureen Kane; C Neill Epperson; Tracy L Bale Journal: Nat Commun Date: 2020-03-20 Impact factor: 14.919