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

doi:10.1007/s00018-021-04068-2

Back

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

Journal article

Open access

Peer reviewed

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, …

Cellular and molecular life sciences : CMLS, Vol.79(1), pp.5-5

12/22/2021

DOI: 10.1007/s00018-021-04068-2

PMCID: PMC9134786

PMID: 34936021

Files and links (1)

url

https://escholarship.org/content/qt18t771qv/qt18t771qv.pdfView

Open Access

Abstract

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. 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. 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.

Comorbidity

Adolescent

Adult

Aged

Aged, 80 and over

Base Sequence

Chemotaxis

Cocaine - pharmacology

Extracellular Vesicles - metabolism

Gene Regulatory Networks

HIV Infections - genetics

Humans

MicroRNAs - genetics

MicroRNAs - metabolism

Middle Aged

Monocytes - metabolism

Proteome - metabolism

Semen - metabolism

Young Adult

Details

Title: Subtitle: 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
Creators: Hussein Kaddour - Stony Brook University
Steven Kopcho - Stony Brook University
Yuan Lyu - Stony Brook University
Nadia Shouman - Stony Brook University
Victor Paromov - Meharry Medical College
Siddharth Pratap - Meharry Medical College
Chandravanu Dash - Meharry Medical College
Eun-Young Kim - Northwestern University
Jeremy Martinson - University of Pittsburgh
Heather McKay - Johns Hopkins University
Marta Epeldegui - David Geffen School of Medicine at UCLA
Joseph B Margolick - Johns Hopkins University
Jack T Stapleton - University of Iowa
Chioma M Okeoma - Stony Brook University
Resource Type: Journal article
Publication Details: Cellular and molecular life sciences : CMLS, Vol.79(1), pp.5-5
DOI: 10.1007/s00018-021-04068-2
PMID: 34936021
PMCID: PMC9134786
NLM abbreviation: Cell Mol Life Sci
ISSN: 1420-682X
eISSN: 1420-9071
Grant note: R21 DA053643 / NIDA NIH HHS R56 AI122960 / NIAID NIH HHS R25 AI164610 / NIAID NIH HHS R01 AI136740 / NIAID NIH HHS R24 DA021471 / NIDA NIH HHS DA042348 / NIH HHS R01 DA050169 / NIDA NIH HHS R24 DA036420 / NIDA NIH HHS DA050169 / NIH HHS DA053643 / NIH HHS R01 DA042348 / NIDA NIH HHS
Language: English
Date published: 12/22/2021
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9984297317202771

Metrics

14 Record Views

11 Times Cited - Web of Science

See more details