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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

Lyu, Yuan and Kaddour, Hussein and Kopcho, Steven and Panzner, Tyler D. and Shouman, Nadia and Kim, Eun-Young and Martinson, Jeremy and McKay, Heather and Martinez-Maza, Otoniel and Margolick, Joseph B. and Stapleton, Jack T. and Okeoma, Chioma M. (2019) 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. Cells, 8 (9). p. 1027. ISSN 2073-4409

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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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lyu, Yuan
Kaddour, Hussein
Kopcho, Steven
Panzner, Tyler D.
Shouman, Nadia
Kim, Eun-Young
Martinson, Jeremyjmartins@pitt.edujmartins
McKay, Heather
Martinez-Maza, Otoniel
Margolick, Joseph B.
Stapleton, Jack T.
Okeoma, Chioma M.
Date: 2019
Date Type: Publication
Journal or Publication Title: Cells
Volume: 8
Number: 9
Publisher: MDPI AG
Page Range: p. 1027
DOI or Unique Handle: 10.3390/cells8091027
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
Uncontrolled Keywords: semen exosomes, monocytes, actin reorganization, psychostimulants, chemotaxis, morphometrics
ISSN: 2073-4409
Official URL: http://dx.doi.org/10.3390/cells8091027
Funders: National Institute on Drug Abuse
Article Type: Research Article
Date Deposited: 01 Jul 2021 14:27
Last Modified: 01 Jul 2021 14:27
URI: http://d-scholarship.pitt.edu/id/eprint/41307

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