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Viruses
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Viruses and Extracellular Vesicles 2.0
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Viruses and Extracellular Vesicles 2.0

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 18323

Special Issue Editor

Dr. Chioma M. Okeoma

E-Mail Website
Guest Editor
Department of Pharmacology, Stony Brook University, Stony Brook, NY 11794-8651, USA
Interests: HIV; extracellular vesicles; cancer; restriction factors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) is a generic name that describes a heterogeneous collection of membranous vesicles, which includes ectosomes, exosomes, microvesicles, microparticles, oncosomes, and prostasomes, which are released by almost all cell types. Contrary to the previously thought role for EVs―a mechanism to discard non-functional cellular components, various studies have shown that EVs are vehicles through which biologically active molecules can be disseminated to local or distal sites to mediate specific biological roles.

Given the diversity and complexity of EV biogenesis and cargo, it is no secret that EVs and viruses, especially enveloped RNA viruses, have much more in common than previously appreciated. For example, EVs and some viruses are similar in size and have a similar biogenesis. Moreover, EVs from virus-infected cells incorporate both host- and virus-encoded molecules. Thus, with the increase in EV diversity, interest in EV function, EV utility, and their role in physiological and pathophysiological processes has increased. However, the differing features of EVs and viruses, and identifying characteristics dependent on originating cell types, remain largely unknown.

In this Special Issue of Viruses, we want to highlight findings from cutting edge research on the interaction of EVs and viruses from the divergent body of professionals involved in EV/virology research. Of particular interest are studies on the interaction of EVs and viruses in plants, animals, or human hosts. We also invite manuscripts that discus viruses that are likely to respond to EV-based therapy. In addition, this Special Issue focuses on recent findings, knowledge gaps, and perspectives on the following:

  1. The biological implications of the broad EV size diversity and how to distinguish EVs from viral particles;
  2. The role of EV and virus biogenesis pathway in their composition and contribution to biology;
  3. Clinical and translational studies that characterize EV subpopulations and phenotypes under physiological or pathophysiological conditions;
  4. Studies on the compositional properties of EVs released by healthy and virally infected cells, carrying virally encoded molecules or viral particles;
  5. Studies focusing on separating infectious viruses (HIV and other small RNA viruses) from noninfectious EVs carrying viral products (proteins and nucleic acids);
  6. Studies that focus on how noninfectious EVs positively or negatively regulate viral infection;
  7. Studies that manipulate EVs as a means to inhibit viral infection;
  8. Implementation studies focused on applying EVs in therapeutics development.

Dr. Chioma M. Okeoma
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Extracellular vesicles
  • Exosomes
  • Viruses
  • Microvesicles

Related Special Issues

Published Papers (5 papers)

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Research

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18 pages, 3897 KiB  
Article
Methamphetamine Induces the Release of Proadhesive Extracellular Vesicles and Promotes Syncytia Formation: A Potential Role in HIV-1 Neuropathogenesis
by Subhash Chand, Catherine DeMarino, Austin Gowen, Maria Cowen, Sarah Al-Sharif, Fatah Kashanchi and Sowmya V. Yelamanchili
Viruses 2022, 14(3), 550; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030550 - 07 Mar 2022
Cited by 5 | Viewed by 2950
Abstract
Despite the success of combinational antiretroviral therapy (cART), the high pervasiveness of human immunodeficiency virus-1 (HIV)-associated neurocognitive disorders (HAND) poses a significant challenge for society. Methamphetamine (meth) and related amphetamine compounds, which are potent psychostimulants, are among the most commonly used illicit drugs. [...] Read more.
Despite the success of combinational antiretroviral therapy (cART), the high pervasiveness of human immunodeficiency virus-1 (HIV)-associated neurocognitive disorders (HAND) poses a significant challenge for society. Methamphetamine (meth) and related amphetamine compounds, which are potent psychostimulants, are among the most commonly used illicit drugs. Intriguingly, HIV-infected individuals who are meth users have a comparatively higher rate of neuropsychological impairment and exhibit a higher viral load in the brain than infected individuals who do not abuse meth. Effectively, all cell types secrete nano-sized lipid membrane vesicles, referred to as extracellular vesicles (EVs) that can function as intercellular communication to modulate the physiology and pathology of the cells. This study shows that meth treatments on chronically HIV-infected promonocytic U1 cells induce the release of EVs that promote cellular clustering and syncytia formation, a phenomenon that facilitates HIV pathogenesis. Our analysis also revealed that meth exposure increased intercellular adhesion molecule-1 (ICAM-1) and HIV-Nef protein expression in both large (10 K) and small (100 K) EVs. Further, when meth EVs are applied to uninfected naïve monocyte-derived macrophages (MDMs), we saw a significant increase in cell clustering and syncytia formation. Furthermore, treatment of MDMs with antibodies against ICAM-1 and its receptor, lymphocyte function-associated antigen 1 (LFA1), substantially blocked syncytia formation, and consequently reduced the number of multinucleated cells. In summary, our findings reveal that meth exacerbates HIV pathogenesis in the brain through release of proadhesive EVs, promoting syncytia formation and thereby aiding in the progression of HIV infection in uninfected cells. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles 2.0)
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24 pages, 2483 KiB  
Article
Characterization of Extracellular Vesicles Secreted in Lentiviral Producing HEK293SF Cell Cultures
by Aline Do Minh, Alexandra T. Star, Jacek Stupak, Kelly M. Fulton, Arsalan S. Haqqani, Jean-François Gélinas, Jianjun Li, Susan M. Twine and Amine A. Kamen
Viruses 2021, 13(5), 797; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050797 - 29 Apr 2021
Cited by 6 | Viewed by 3447
Abstract
Lentiviral vectors (LVs) are a powerful tool for gene and cell therapy and human embryonic kidney cells (HEK293) have been extensively used as a platform for production of these vectors. Like most cells and cellular tissues, HEK293 cells release extracellular vesicles (EVs). EVs [...] Read more.
Lentiviral vectors (LVs) are a powerful tool for gene and cell therapy and human embryonic kidney cells (HEK293) have been extensively used as a platform for production of these vectors. Like most cells and cellular tissues, HEK293 cells release extracellular vesicles (EVs). EVs released by cells share similar size, biophysical characteristics and even a biogenesis pathway with cell-produced enveloped viruses, making it a challenge to efficiently separate EVs from LVs. Thus, EVs co-purified with LVs during downstream processing, are considered “impurities” in the context of gene and cell therapy. A greater understanding of EVs co-purifying with LVs is needed to enable improved downstream processing. To that end, EVs from an inducible lentivirus producing cell line were studied under two conditions: non-induced and induced. EVs were identified in both conditions, with their presence confirmed by transmission electron microscopy and Western blot. EV cargos from each condition were then further characterized by a multi-omic approach. Nineteen proteins were identified by mass spectrometry as potential EV markers to differentiate EVs in LV preparations. Lipid composition of EV preparations before and after LV induction showed similar enrichment in phosphatidylserine. RNA cargos in EVs showed enrichment in transcripts involved in viral processes and binding functions. These findings provide insights on the product profile of lentiviral preparations and could support the development of improved separation strategies aimed at removing co-produced EVs. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles 2.0)
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19 pages, 6377 KiB  
Article
Epstein-Barr Virus LMP1 Modulates the CD63 Interactome
by Mujeeb Cheerathodi, Dingani Nkosi, Allaura S. Cone, Sara B. York and David G. Meckes, Jr.
Viruses 2021, 13(4), 675; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040675 - 15 Apr 2021
Cited by 11 | Viewed by 3604
Abstract
Tetraspanin CD63 is a cluster of cell surface proteins with four transmembrane domains; it is associated with tetraspanin-enriched microdomains and typically localizes to late endosomes and lysosomes. CD63 plays an important role in the cellular trafficking of different proteins, EV cargo sorting, and [...] Read more.
Tetraspanin CD63 is a cluster of cell surface proteins with four transmembrane domains; it is associated with tetraspanin-enriched microdomains and typically localizes to late endosomes and lysosomes. CD63 plays an important role in the cellular trafficking of different proteins, EV cargo sorting, and vesicle formation. We have previously shown that CD63 is important in LMP1 trafficking to EVs, and this also affects LMP1-mediated intracellular signaling including MAPK/ERK, NF-κB, and mTOR activation. Using the BioID method combined with mass spectrometry, we sought to define the broad CD63 interactome and how LMP1 modulates this network of interacting proteins. We identified a total of 1600 total proteins as a network of proximal interacting proteins to CD63. Biological process enrichment analysis revealed significant involvement in signal transduction, cell communication, protein metabolism, and transportation. The CD63-only interactome was enriched in Rab GTPases, SNARE proteins, and sorting nexins, while adding LMP1 into the interactome increased the presence of signaling and ribosomal proteins. Our results showed that LMP1 alters the CD63 interactome, shifting the network of protein enrichment from protein localization and vesicle-mediated transportation to metabolic processes and translation. We also show that LMP1 interacts with mTOR, Nedd4 L, and PP2A, indicating the formation of a multiprotein complex with CD63, thereby potentially regulating LMP1-dependent mTOR signaling. Collectively, the comprehensive analysis of CD63 proximal interacting proteins provides insights into the network of partners required for endocytic trafficking and extracellular vesicle cargo sorting, formation, and secretion. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles 2.0)
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Review

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22 pages, 3300 KiB  
Review
The Past, the Present, and the Future of the Size Exclusion Chromatography in Extracellular Vesicles Separation
by Hussein Kaddour, Malik Tranquille and Chioma M. Okeoma
Viruses 2021, 13(11), 2272; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112272 - 13 Nov 2021
Cited by 20 | Viewed by 3745
Abstract
Extracellular vesicles (EVs) are cell-derived membranous particles secreted by all cell types (including virus infected and uninfected cells) into the extracellular milieu. EVs carry, protect, and transport a wide array of bioactive cargoes to recipient/target cells. EVs regulate physiological and pathophysiological processes in [...] Read more.
Extracellular vesicles (EVs) are cell-derived membranous particles secreted by all cell types (including virus infected and uninfected cells) into the extracellular milieu. EVs carry, protect, and transport a wide array of bioactive cargoes to recipient/target cells. EVs regulate physiological and pathophysiological processes in recipient cells and are important in therapeutics/drug delivery. Despite these great attributes of EVs, an efficient protocol for EV separation from biofluids is lacking. Numerous techniques have been adapted for the separation of EVs with size exclusion chromatography (SEC)-based methods being the most promising. Here, we review the SEC protocols used for EV separation, and discuss opportunities for significant improvements, such as the development of novel particle purification liquid chromatography (PPLC) system capable of tandem purification and characterization of biological and synthetic particles with near-single vesicle resolution. Finally, we identify future perspectives and current issues to make PPLC a tool capable of providing a unified, automated, adaptable, yet simple and affordable particle separation resource. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles 2.0)
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33 pages, 854 KiB  
Review
Extracellular Vesicles in HTLV-1 Communication: The Story of an Invisible Messenger
by Sarah Al Sharif, Daniel O. Pinto, Gifty A. Mensah, Fatemeh Dehbandi, Pooja Khatkar, Yuriy Kim, Heather Branscome and Fatah Kashanchi
Viruses 2020, 12(12), 1422; https://0-doi-org.brum.beds.ac.uk/10.3390/v12121422 - 10 Dec 2020
Cited by 9 | Viewed by 3819
Abstract
Human T-cell lymphotropic virus type 1 (HTLV-1) infects 5–10 million people worldwide and is the causative agent of adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as other inflammatory diseases. A major concern is that the most majority of [...] Read more.
Human T-cell lymphotropic virus type 1 (HTLV-1) infects 5–10 million people worldwide and is the causative agent of adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as other inflammatory diseases. A major concern is that the most majority of individuals with HTLV-1 are asymptomatic carriers and that there is limited global attention by health care officials, setting up potential conditions for increased viral spread. HTLV-1 transmission occurs primarily through sexual intercourse, blood transfusion, intravenous drug usage, and breast feeding. Currently, there is no cure for HTLV-1 infection and only limited treatment options exist, such as class I interferons (IFN) and Zidovudine (AZT), with poor prognosis. Recently, small membrane-bound structures, known as extracellular vesicles (EVs), have received increased attention due to their potential to carry viral cargo (RNA and proteins) in multiple pathogenic infections (i.e., human immunodeficiency virus type I (HIV-1), Zika virus, and HTLV-1). In the case of HTLV-1, EVs isolated from the peripheral blood and cerebral spinal fluid (CSF) of HAM/TSP patients contained the viral transactivator protein Tax. Additionally, EVs derived from HTLV-1-infected cells (HTLV-1 EVs) promote functional effects such as cell aggregation which enhance viral spread. In this review, we present current knowledge surrounding EVs and their potential role as immune-modulating agents in cancer and other infectious diseases such as HTLV-1 and HIV-1. We discuss various features of EVs that make them prime targets for possible vehicles of future diagnostics and therapies. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles 2.0)
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