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J Acquir Immune Defic Syndr. 2020 Jan 1;83(1):90-98. doi: 10.1097/QAI.0000000000002233.

Semen Extracellular Vesicles From HIV-1-Infected Individuals Inhibit HIV-1 Replication In Vitro, and Extracellular Vesicles Carry Antiretroviral Drugs In Vivo.

Author information

1
Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA.
2
Medical Service, Iowa City Veterans Affairs Medical Center, Iowa City, IA.
3
Department of Pharmacology, Stony Brook University School of Medicine, Stony Brook, NY.
4
Antiviral Pharmacology Laboratory, College of Pharmacy, UNMC Center for Drug Discovery, University of Nebraska Medical Center, Omaha, NE.

Abstract

BACKGROUND:

Extracellular vesicles (EVs) are cell-derived vesicles with diverse functions in intercellular communication including disease and infection, and EVs seem to influence HIV-1 pathogenesis. EVs isolated from HIV-1-uninfected semen (SE), but not blood (BE), contain factors that interfere with HIV-1 infection and replication in target cells. The reason for this dichotomy is unknown. Furthermore, the effect of HIV-1 infection and antiretroviral (ARV) drugs on the anti-HIV-1 effects of SE and BE is unknown. Here, we characterize EVs and EV-free plasma isolated from HIV-infected donor semen and blood and their effects on HIV infection.

METHODS:

EVs and EV-free plasma were purified from autologous blood and semen of HIV-negative, HIV-infected antiretroviral therapy (ART)-naïve, and HIV-infected ART-treated participants. HIV infection was assessed in a TZM-bl cell reporter system. ARV concentrations were analyzed using liquid chromatography-mass spectrometry.

RESULTS:

SE isolated from both HIV-negative and HIV-infected, ART-naïve donors inhibited HIV-1 infection, but BE and semen and blood EV-free plasma did not. By contrast, BE, SE, and EV-free plasma from HIV-infected, ART-treated donors inhibited HIV-1. Importantly, exosomes isolated from ART-treated donors contained concentrations of ARV drugs (ART-EVs) at biologically relevant inhibitory levels.

CONCLUSIONS:

The HIV-1-inhibitory phenotype of SE is independent of donor HIV-1 or ART status, and ARV drugs and their metabolites are SE- and BE-associated in vivo.

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