Extracellular Vesicles: A Key Player in HIV-1 Infection and Disease Progression

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 10370

Special Issue Editor

1. Microbiology Program, Alabama State University, Montgomery, AL 36104, USA
2. Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA
Interests: exosomes; HIV; adenovirus; Pseudomonas
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues:

Human immunodeficiency virus-1 is one of the most studied retroviruses; however, there is still a wealth of information to be learned about the virus’ entry, lifecycle, and pathogenesis. The role of extracellular vesicles (EVs) in HIV-1 entry and pathogenesis are beginning to be appreciated. EVs are secreted from all cell types (e.g., T cells, mast cells, stem cells, microglia, and endothelial cells) and are in many biological fluids (e.g., blood, saliva, breast milk, and urine). EVs range in size, and these vehicles traffic nucleic acids (RNA, microRNA, and DNA), proteins, and lipids. EVs can serve in communication to promote disease transmission, progression, and/or to protect the host.

Viruses are complex organisms that may have a parasitic, symbiotic, and/or therapeutic relationship with host systems. These parasitic and symbiotic relationships are continuously evolving. Understanding molecular and immunological signatures involved in EV biogenesis and composition could enable the development of new or improved diagnostic, intervention, and/or therapeutic tools. This Special Issue will cover the investigation of EVs for the implementation of HIV-1 diagnostics, vaccine tools, and therapeutic tools. This Special Issue is in line with the current literature, and will add to new knowledge.

We would like to receive contributions related to but not limited to:

-The impact of EVs (exosomes, microvesicles, apoptotic bodies, large oncosomes) on HIV-1 pathogenesis on in vitro and in vivo systems.

-The impact of substance abuse on EVs and HIV-1 pathogenesis.

-The implementation of EVs for the development of novel diagnostic tools and/or HIV-1 vaccine development. Researchers are welcome to contribute reviews/mini reviews, original research, or method articles.

Dr. Qiana Matthews
Guest Editor

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Keywords

  • human immunodeficiency virus-1
  • extracellular vesicles
  • biological fluids
  • viral infections
  • diagnostics
  • biomarkers
  • vaccines

Published Papers (3 papers)

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Research

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21 pages, 21961 KiB  
Article
Velocity Gradient Separation Reveals a New Extracellular Vesicle Population Enriched in miR-155 and Mitochondrial DNA
by Myriam Vaillancourt, Audrey Hubert, Caroline Subra, Julien Boucher, Wilfried Wenceslas Bazié, Julien Vitry, Sofiane Berrazouane, Jean-Pierre Routy, Sylvie Trottier, Cécile Tremblay, Mohammad-Ali Jenabian, Abderrahim Benmoussa, Patrick Provost, Philippe A. Tessier and Caroline Gilbert
Pathogens 2021, 10(5), 526; https://doi.org/10.3390/pathogens10050526 - 27 Apr 2021
Cited by 5 | Viewed by 3995
Abstract
Extracellular vesicles (EVs) and their contents (proteins, lipids, messenger RNA, microRNA, and DNA) are viewed as intercellular signals, cell-transforming agents, and shelters for viruses that allow both diagnostic and therapeutic interventions. EVs circulating in the blood of individuals infected with human immunodeficiency virus [...] Read more.
Extracellular vesicles (EVs) and their contents (proteins, lipids, messenger RNA, microRNA, and DNA) are viewed as intercellular signals, cell-transforming agents, and shelters for viruses that allow both diagnostic and therapeutic interventions. EVs circulating in the blood of individuals infected with human immunodeficiency virus (HIV-1) may provide insights into pathogenesis, inflammation, and disease progression. However, distinguishing plasma membrane EVs from exosomes, exomeres, apoptotic bodies, virions, and contaminating proteins remains challenging. We aimed at comparing sucrose and iodixanol density and velocity gradients along with commercial kits as a means of separating EVs from HIV particles and contaminating protein like calprotectin; and thereby evaluating the suitability of current plasma EVs analysis techniques for identifying new biomarkers of HIV-1 immune activation. Multiple analysis have been performed on HIV-1 infected cell lines, plasma from HIV-1 patients, or plasma from HIV-negative individuals spiked with HIV-1. Commercial kits, the differential centrifugation and density or velocity gradients to precipitate and separate HIV, EVs, and proteins such as calprotectin, have been used. EVs, virions, and contaminating proteins were characterized using Western blot, ELISA, RT-PCR, hydrodynamic size measurement, and enzymatic assay. Conversely to iodixanol density or velocity gradient, protein and virions co-sedimented in the same fractions of the sucrose density gradient than AChE-positive EVs. Iodixanol velocity gradient provided the optimal separation of EVs from viruses and free proteins in culture supernatants and plasma samples from a person living with HIV (PLWH) or a control and revealed a new population of large EVs enriched in microRNA miR-155 and mitochondrial DNA. Although EVs and their contents provide helpful information about several key events in HIV-1 pathogenesis, their purification and extensive characterization by velocity gradient must be investigated thoroughly before further use as biomarkers. By revealing a new population of EVs enriched in miR-155 and mitochondrial DNA, this study paves a way to increase our understanding of HIV-1 pathogenesis. Full article
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18 pages, 1463 KiB  
Article
Diurnal Variation of Plasma Extracellular Vesicle Is Disrupted in People Living with HIV
by Wilfried Wenceslas Bazié, Benjamin Goyer, Julien Boucher, Yuwei Zhang, Delphine Planas, Debashree Chatterjee, Jean-Pierre Routy, Michel Alary, Petronela Ancuta and Caroline Gilbert
Pathogens 2021, 10(5), 518; https://doi.org/10.3390/pathogens10050518 - 24 Apr 2021
Cited by 5 | Viewed by 2188
Abstract
Background: Several types of extracellular vesicles (EVs) secreted by various immune and non-immune cells are present in the human plasma. We previously demonstrated that EV abundance and microRNA content change in pathological conditions, such as HIV infection. Here, we investigated daily variations of [...] Read more.
Background: Several types of extracellular vesicles (EVs) secreted by various immune and non-immune cells are present in the human plasma. We previously demonstrated that EV abundance and microRNA content change in pathological conditions, such as HIV infection. Here, we investigated daily variations of large and small EVs, in terms of abundance and microRNA contents in people living with HIV (PLWH) receiving antiretroviral therapy (HIV+ART) and uninfected controls (HIV−). Methods: Venous blood samples from n = 10 HIV+ART and n = 10 HIV− participants were collected at 10:00 and 22:00 the same day. Large and small plasma EVs were purified, counted, and the mature miRNAs miR-29a, miR-29b, miR-92, miR-155, and miR-223 copies were measured by RT-PCR. Results: Large EVs were significantly bigger in the plasma collected at 10:00 versus 22:00 in both groups. There was a significant day–night increase in the quantity of 5 miRNAs in HIV− large EVs. In HIV+ART, only miR-155 daily variation has been observed in large EVs. Finally, EV-miRNA content permits to distinguish HIV− to HIV+ART in multivariate analysis. Conclusion: These results point that plasma EV amount and microRNA contents are under daily variation in HIV− people. This new dynamic measure is disrupted in PLWH despite viral-suppressive ART. This study highlights a significant difference concerning EV abundance and their content measured at 22:00 between both groups. Therefore, the time of blood collection must be considered in the future for the EV as biomarkers. Full article
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Review

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20 pages, 913 KiB  
Review
Extracellular Vesicles: Roles in Human Viral Infections, Immune-Diagnostic, and Therapeutic Applications
by Ayodeji O. Ipinmoroti and Qiana L. Matthews
Pathogens 2020, 9(12), 1056; https://doi.org/10.3390/pathogens9121056 - 17 Dec 2020
Cited by 32 | Viewed by 3439
Abstract
Membrane-bound vesicles that are released from cells are increasingly being studied as a medium of intercellular communication, as these act to shuttle functional proteins, such as lipids, DNA, rRNA, and miRNA, between cells during essential physiological processes. Extracellular vesicles (EVs), most commonly exosomes, [...] Read more.
Membrane-bound vesicles that are released from cells are increasingly being studied as a medium of intercellular communication, as these act to shuttle functional proteins, such as lipids, DNA, rRNA, and miRNA, between cells during essential physiological processes. Extracellular vesicles (EVs), most commonly exosomes, are consistently produced by virus-infected cells, and they play crucial roles in mediating communication between infected and uninfected cells. Notably, pathophysiological roles for EVs have been established in various viral infections, including human immune deficiency virus (HIV), coronavirus (CoV), and human adenovirus (HAdv). Retroviruses, such as HIV, modulate the production and composition of EVs, and critically, these viruses can exploit EV formation, secretion, and release pathways to promote infection, transmission, and intercellular spread. Consequently, EV production has been investigated as a potential tool for the development of improved viral infection diagnostics and therapeutics. This review will summarize our present knowledge of EV–virus relationships, focusing on their known roles in pathophysiological pathways, immunomodulatory mechanisms, and utility for biomarker discovery. This review will also discuss the potential for EVs to be exploited as diagnostic and treatment tools for viral infection. Full article
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