Journal article
Semen Extracellular Vesicles From HIV-1-Infected Individuals Inhibit HIV-1 Replication In Vitro, and Extracellular Vesicles Carry Antiretroviral Drugs In Vivo
Journal of acquired immune deficiency syndromes (1999), Vol.83(1), pp.90-98
01/01/2020
DOI: 10.1097/QAI.0000000000002233
PMCID: PMC7144830
PMID: 31809364
Abstract
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.
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.
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.
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.
Details
- Title: Subtitle
- Semen Extracellular Vesicles From HIV-1-Infected Individuals Inhibit HIV-1 Replication In Vitro, and Extracellular Vesicles Carry Antiretroviral Drugs In Vivo
- Creators
- Jennifer L Welch - University of IowaHussein Kaddour - Stony Brook UniversityLee Winchester - University of Nebraska Medical CenterCourtney V Fletcher - University of Nebraska Medical CenterJack T Stapleton - University of IowaChioma M Okeoma - Stony Brook University
- Resource Type
- Journal article
- Publication Details
- Journal of acquired immune deficiency syndromes (1999), Vol.83(1), pp.90-98
- DOI
- 10.1097/QAI.0000000000002233
- PMID
- 31809364
- PMCID
- PMC7144830
- ISSN
- 1525-4135
- eISSN
- 1944-7884
- Grant note
- T32 AI007343 / NIAID NIH HHS I01 BX000207 / BLRD VA R01 AI124965 / NIAID NIH HHS R01 DA042348 / NIDA NIH HHS T32 AI007533 / NIAID NIH HHS
- Language
- English
- Date published
- 01/01/2020
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984297317802771
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