Human Immunodeficiency Virus (HIV) Infection and Use of Illicit Substances Promote Secretion of Semen Exosomes that Enhance Monocyte Adhesion and Induce Actin Reorganization and Chemotactic Migration

Yuan Lyu; Hussein Kaddour; Steven Kopcho; Tyler D Panzner; Nadia Shouman; Eun-Young Kim; Jeremy Martinson; Heather McKay; Otoniel Martinez-Maza; Joseph B Margolick; Jack T Stapleton; Chioma M Okeoma

doi:10.3390/cells8091027

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Human Immunodeficiency Virus (HIV) Infection and Use of Illicit Substances Promote Secretion of Semen Exosomes that Enhance Monocyte Adhesion and Induce Actin Reorganization and Chemotactic Migration

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Human Immunodeficiency Virus (HIV) Infection and Use of Illicit Substances Promote Secretion of Semen Exosomes that Enhance Monocyte Adhesion and Induce Actin Reorganization and Chemotactic Migration

Yuan Lyu, Hussein Kaddour, Steven Kopcho, Tyler D Panzner, Nadia Shouman, Eun-Young Kim, Jeremy Martinson, Heather McKay, Otoniel Martinez-Maza, Joseph B Margolick, …

Cells (Basel, Switzerland), Vol.8(9), p.1027

09/03/2019

DOI: 10.3390/cells8091027

PMCID: PMC6770851

PMID: 31484431

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Abstract

Semen exosomes (SE) from HIV-uninfected (HIV-) individuals potently inhibit HIV infection in vitro. However, morphological changes in target cells in response to SE have not been characterized or have the effect of HIV infection or the use of illicit substances, specifically psychostimulants, on the function of SE been elucidated. The objective of this study was to evaluate the effect of HIV infection, psychostimulant use, and both together on SE-mediated regulation of monocyte function. SE were isolated from semen of HIV- and HIV-infected (HIV+) antiretroviral therapy (ART)-naive participants who reported either using or not using psychostimulants. The SE samples were thus designated as HIV-Drug-, HIV-Drug+, HIV+Drug-, and HIV+Drug+. U937 monocytes were treated with different SEs and analyzed for changes in transcriptome, morphometrics, actin reorganization, adhesion, and chemotaxis. HIV infection and/or use of psychostimulants had minimal effects on the physical characteristics of SE. However, different SEs had diverse effects on the messenger RNA signature of monocytes and rapidly induced monocyte adhesion and spreading. SE from HIV infected or psychostimulants users but not HIV-Drug- SE, stimulated actin reorganization, leading to the formation of filopodia-like structures and membrane ruffles containing F-actin and vinculin that in some cases were colocalized. All SE stimulated monocyte chemotaxis to HIV secretome and activated the secretion of matrix metalloproteinases, a phenotype exacerbated by HIV infection and psychostimulant use. SE-directed regulation of cellular morphometrics and chemotaxis depended on the donor clinical status because HIV infection and psychostimulant use altered SE function. Although our inclusion criteria specified the use of cocaine, humans are poly-drug and alcohol users and our study participants used psychostimulants, marijuana, opiates, and alcohol. Thus, it is possible that the effects observed in this study may be due to one of these other substances or due to an interaction between different substances.

Actins - metabolism

Adult

Cell Adhesion

Chemotaxis

Cocaine-Related Disorders - complications

Cocaine-Related Disorders - metabolism

Exosomes - metabolism

HIV Infections - complications

HIV Infections - metabolism

Humans

Male

Matrix Metalloproteinases - metabolism

Monocytes - metabolism

Monocytes - physiology

Semen - metabolism

Transcriptome

U937 Cells

Details

Title: Subtitle: Human Immunodeficiency Virus (HIV) Infection and Use of Illicit Substances Promote Secretion of Semen Exosomes that Enhance Monocyte Adhesion and Induce Actin Reorganization and Chemotactic Migration
Creators: Yuan Lyu - Stony Brook University
Hussein Kaddour - Stony Brook University
Steven Kopcho - Stony Brook University
Tyler D Panzner - Stony Brook University
Nadia Shouman - Stony Brook University
Eun-Young Kim - Northwestern University
Jeremy Martinson - University of Pittsburgh
Heather McKay - Johns Hopkins University
Otoniel Martinez-Maza - University of California, Los Angeles
Joseph B Margolick - Johns Hopkins University
Jack T Stapleton - University of Iowa
Chioma M Okeoma - Stony Brook University
Resource Type: Journal article
Publication Details: Cells (Basel, Switzerland), Vol.8(9), p.1027
DOI: 10.3390/cells8091027
PMID: 31484431
PMCID: PMC6770851
NLM abbreviation: Cells
ISSN: 2073-4409
eISSN: 2073-4409
Grant note: U01 AI035039 / NIAID NIH HHS T32 GM007518 / NIGMS NIH HHS U01 AI035041 / NIAID NIH HHS U01 AI035040 / NIAID NIH HHS UM1 AI035043 / NIAID NIH HHS T32 AI007343 / NIAID NIH HHS U01 AI035042 / NIAID NIH HHS I01 BX000207 / BLRD VA U01 HL146201 / NHLBI NIH HHS UL1 TR001079 / NCATS NIH HHS R01 DA042348 / NIDA NIH HHS
Language: English
Date published: 09/03/2019
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9984297331602771

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