Viruses and Extracellular Vesicles

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

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 78142

Special Issue Editor


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Guest Editor
Department of Pharmacology, Stony Brook University, Stony Brook, NY 11794-8651, USA
Interests: HIV; extracellular vesicles; cancer; restriction factors
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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

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Keywords

  • Extracellular vesicles
  • Exosomes
  • Viruses
  • Microvesicles

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Published Papers (14 papers)

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Editorial

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3 pages, 174 KiB  
Editorial
Viruses and Extracellular Vesicles: Special Issue, 2020, with Thirteen Articles by Chioma M. Okeoma
by Chioma M. Okeoma
Viruses 2020, 12(11), 1265; https://doi.org/10.3390/v12111265 - 6 Nov 2020
Cited by 1 | Viewed by 2046
Abstract
The discovery of extracellular vesicles (EVs) dates back to the early 1940s, when Erwin Chargaff and Randolph West showed that platelet-free plasma contains coagulation components that pellet upon high-speed (31,000× g) centrifugation [...] Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)

Research

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22 pages, 4807 KiB  
Article
Electrostatic Surface Properties of Blood and Semen Extracellular Vesicles: Implications of Sialylation and HIV-Induced Changes on EV Internalization
by Hussein Kaddour, Tyler D. Panzner, Jennifer L. Welch, Nadia Shouman, Mahesh Mohan, Jack T. Stapleton and Chioma M. Okeoma
Viruses 2020, 12(10), 1117; https://doi.org/10.3390/v12101117 - 1 Oct 2020
Cited by 20 | Viewed by 3947
Abstract
Although extracellular vesicle (EV) surface electrostatic properties (measured as zeta potential, ζ-potential) have been reported by many investigators, the biophysical implications of charge and EV origin remains uncertain. Here, we compared the ζ-potential of human blood EVs (BEVs) and semen EVs (SEVs) from [...] Read more.
Although extracellular vesicle (EV) surface electrostatic properties (measured as zeta potential, ζ-potential) have been reported by many investigators, the biophysical implications of charge and EV origin remains uncertain. Here, we compared the ζ-potential of human blood EVs (BEVs) and semen EVs (SEVs) from 26 donors that were HIV-infected (HIV+, n = 13) or HIV uninfected (HIV-, n = 13). We found that, compared to BEVs that bear neutral surface charge, SEVs were significantly more negatively charged, even when BEVs and SEVs were from the same individual. Comparison of BEVs and SEVs from HIV- and HIV+ groups revealed subtle HIV-induced alteration in the ζ-potential of EVs, with the effect being more significant in SEVs (∆ζ-potential = −8.82 mV, p-value = 0.0062) than BEVs (∆ζ-potential = −1.4 mV, p-value = 0.0462). These observations were validated by differences in the isoelectric point (IEP) of EVs, which was in the order of HIV + SEV ≤ HIV-SEV ≪ HIV + BEV ≤ HIV-BEV. Functionally, the rate and efficiency of SEV internalization by the human cervical epithelial cell line, primary peripheral blood lymphocytes, and primary blood-derived monocytes were significantly higher than those of BEVs. Mechanistically, removal of sialic acids from the surface of EVs using neuraminidase treatment significantly decreased SEV’s surface charge, concomitant with a substantial reduction in SEV’s internalization. The neuraminidase effect was independent of HIV infection and insignificant for BEVs. Finally, these results were corroborated by enrichment of glycoproteins in SEVs versus BEVs. Taken together, these findings uncover fundamental tissue-specific differences in surface electrostatic properties of EVs and highlight the critical role of surface charge in EV/target cell interactions. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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17 pages, 3025 KiB  
Article
Rotaviruses Associate with Distinct Types of Extracellular Vesicles
by Pavel Iša, Arianna Pérez-Delgado, Iván R. Quevedo, Susana López and Carlos F. Arias
Viruses 2020, 12(7), 763; https://doi.org/10.3390/v12070763 - 16 Jul 2020
Cited by 15 | Viewed by 4871
Abstract
Rotaviruses are the leading cause of viral gastroenteritis among children under five years of age. Rotavirus cell entry has been extensively studied; however, rotavirus cell release is still poorly understood. Specifically, the mechanism by which rotaviruses leave the cell before cell lysis is [...] Read more.
Rotaviruses are the leading cause of viral gastroenteritis among children under five years of age. Rotavirus cell entry has been extensively studied; however, rotavirus cell release is still poorly understood. Specifically, the mechanism by which rotaviruses leave the cell before cell lysis is not known. Previous works have found rotavirus proteins and viral particles associated with extracellular vesicles secreted by cells. These vesicles have been shown to contain markers of exosomes; however, in a recent work they presented characteristics more typical of microparticles, and they were associated with an increase in the infectivity of the virus. In this work, we purified different types of vesicles from rotavirus-infected cells. We analyzed the association of virus with these vesicles and their possible role in promotion of rotavirus infection. We confirmed a non-lytic rotavirus release from the two cell lines tested, and observed a notable stimulation of vesicle secretion following rotavirus infection. A fraction of the secreted viral particles present in the cell supernatant was protected from protease treatment, possibly through its association with membranous vesicles; the more pronounced association of the virus was with fractions corresponding to cell membrane generated microvesicles. Using electron microscopy, we found different size vesicles with particles resembling rotaviruses associated from both- the outside and the inside. The viral particles inside the vesicles were refractory to neutralization with a potent rotavirus neutralizing monoclonal antibody, and were able to infect cells even without trypsin activation. The association of rotavirus particles with extracellular vesicles suggests these might have a role in virus spread. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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16 pages, 2350 KiB  
Article
mRNA Profile in Milk Extracellular Vesicles from Bovine Leukemia Virus-Infected Cattle
by Hinata Ishikawa, Md. Matiur Rahman, Marika Yamauchi, Shigeo Takashima, Yoshiko Wakihara, Yuji O. Kamatari, Kaori Shimizu, Ayaka Okada and Yasuo Inoshima
Viruses 2020, 12(6), 669; https://doi.org/10.3390/v12060669 - 20 Jun 2020
Cited by 19 | Viewed by 4433
Abstract
Milk extracellular vesicles (EVs) form an excellent source of mRNAs, microRNAs (miRNAs), proteins, and lipids that represent the physiological and pathological status of the host. Recent studies have reported milk EVs as novel biomarkers for many infectious diseases in both humans and animals. [...] Read more.
Milk extracellular vesicles (EVs) form an excellent source of mRNAs, microRNAs (miRNAs), proteins, and lipids that represent the physiological and pathological status of the host. Recent studies have reported milk EVs as novel biomarkers for many infectious diseases in both humans and animals. For example, miRNAs in milk EVs from cattle were used for early detection of bacterial infection in the mammary gland. Based on these findings, we hypothesized that mRNAs in milk EVs are suitable for gaining a better understanding of the pathogenesis of bovine leukemia virus (BLV) infection and prognosis of the clinical stage in cattle. For that purpose, milk EVs were isolated from BLV-infected and uninfected cattle, and mRNAs were investigated using microarray analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed mainly focusing on the differentially expressed genes (DEGs) in milk EVs from BLV-infected cattle. GO and KEGG analyses suggested the DEGs in milk EVs from BLV-infected cattle had involved in diverse molecular functions, biological processes, and distinct disease-related pathways. The present study suggested that BLV infection causes profound effects on host cellular activity, changing the mRNA expression profile in milk EVs obtained from BLV-infected cattle. Overall, our results suggested that the mRNA profile in milk EVs to be a key factor for monitoring the clinical stage of BLV infection. This is the first report of mRNA profiling of milk EVs obtained from BLV-infected cattle. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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22 pages, 3171 KiB  
Article
Extracellular Vesicle Activation of Latent HIV-1 Is Driven by EV-Associated c-Src and Cellular SRC-1 via the PI3K/AKT/mTOR Pathway
by Robert A. Barclay, Gifty A. Mensah, Maria Cowen, Catherine DeMarino, Yuriy Kim, Daniel O. Pinto, James Erickson and Fatah Kashanchi
Viruses 2020, 12(6), 665; https://doi.org/10.3390/v12060665 - 19 Jun 2020
Cited by 18 | Viewed by 4624
Abstract
HIV-1 is a global health crisis that has infected more than 37 million people. Latent reservoirs throughout the body are a major hurdle when it comes to eradicating the virus. In our previous study, we found that exosomes, a type of extracellular vesicle [...] Read more.
HIV-1 is a global health crisis that has infected more than 37 million people. Latent reservoirs throughout the body are a major hurdle when it comes to eradicating the virus. In our previous study, we found that exosomes, a type of extracellular vesicle (EV), from uninfected cells activate the transcription of HIV-1 in latent infected cells, regardless of combination antiretroviral therapy (cART). In this study, we investigated the specific mechanism behind the EV activation of latent HIV-1. We found that phosphorylated c-Src is present in EVs of various cell lines and has the ability to activate downstream proteins such as EGFR, initiating a signal cascade. EGFR is then able to activate the PI3K/AKT/mTOR pathway, resulting in the activation of STAT3 and SRC-1, culminating in the reversal of HIV-1 latency. This was verified by examining levels of HIV-1 TAR, genomic RNA and HIV-1 Gag p24 protein in cell lines and primary cells. We found that EVs containing c-Src rescued HIV-1 despite the presence of inhibitors, validating the importance of EV-associated c-Src in latent HIV-1 activation. Lastly, we discovered an increased recruitment of p300 and NF-κB in the nucleus of EV-treated infected cells. Collectively, our data suggest that EV-associated c-Src is able to activate latent HIV-1 via the PI3K/AKT/mTOR pathway and SRC-1/p300-driven chromatin remodeling. These findings could aid in designing new strategies to prevent the reactivation of latent HIV-1 in patients under cART. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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27 pages, 4887 KiB  
Article
Alphaherpesvirus gB Homologs Are Targeted to Extracellular Vesicles, but They Differentially Affect MHC Class II Molecules
by Kinga Grabowska, Magda Wąchalska, Małgorzata Graul, Michał Rychłowski, Krystyna Bieńkowska-Szewczyk and Andrea D. Lipińska
Viruses 2020, 12(4), 429; https://doi.org/10.3390/v12040429 - 10 Apr 2020
Cited by 13 | Viewed by 4273
Abstract
Herpesvirus envelope glycoprotein B (gB) is one of the best-documented extracellular vesicle (EVs)-incorporated viral proteins. Regarding the sequence and structure conservation between gB homologs, we asked whether bovine herpesvirus-1 (BoHV-1) and pseudorabies virus (PRV)-encoded gB share the property of herpes simplex-1 (HSV-1) gB [...] Read more.
Herpesvirus envelope glycoprotein B (gB) is one of the best-documented extracellular vesicle (EVs)-incorporated viral proteins. Regarding the sequence and structure conservation between gB homologs, we asked whether bovine herpesvirus-1 (BoHV-1) and pseudorabies virus (PRV)-encoded gB share the property of herpes simplex-1 (HSV-1) gB to be trafficked to EVs and affect major histocompatibility complex (MHC) class II. Our data highlight some conserved and differential features of the three gBs. We demonstrate that mature, fully processed BoHV-1 and PRV gBs localize to EVs isolated from constructed stable cell lines and EVs-enriched fractions from virus-infected cells. gB also shares the ability to co-localize with CD63 and MHC II in late endosomes. However, we report here a differential effect of the HSV-1, BoHV-1, and PRV glycoprotein on the surface MHC II levels, and MHC II loading to EVs in stable cell lines, which may result from their adverse ability to bind HLA-DR, with PRV gB being the most divergent. BoHV-1 and HSV-1 gB could retard HLA-DR exports to the plasma membrane. Our results confirm that the differential effect of gB on MHC II may require various mechanisms, either dependent on its complex formation or on inducing general alterations to the vesicular transport. EVs from virus-infected cells also contained other viral glycoproteins, like gD or gE, and they were enriched in MHC II. As shown for BoHV-1 gB- or BoHV-1-infected cell-derived vesicles, those EVs could bind anti-virus antibodies in ELISA, which supports the immunoregulatory potential of alphaherpesvirus gB. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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Review

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23 pages, 714 KiB  
Review
Extracellular Vesicles in Viral Replication and Pathogenesis and Their Potential Role in Therapeutic Intervention
by Asit Kumar, Sunitha Kodidela, Erene Tadrous, Theodore James Cory, Crystal Martin Walker, Amber Marie Smith, Ahona Mukherjee and Santosh Kumar
Viruses 2020, 12(8), 887; https://doi.org/10.3390/v12080887 - 13 Aug 2020
Cited by 26 | Viewed by 8034
Abstract
Extracellular vesicles (EVs) have shown their potential as a carrier of molecular information, and they have been involved in physiological functions and diseases caused by viral infections. Virus-infected cells secrete various lipid-bound vesicles, including endosome pathway-derived exosomes and microvesicles/microparticles that are released from [...] Read more.
Extracellular vesicles (EVs) have shown their potential as a carrier of molecular information, and they have been involved in physiological functions and diseases caused by viral infections. Virus-infected cells secrete various lipid-bound vesicles, including endosome pathway-derived exosomes and microvesicles/microparticles that are released from the plasma membrane. They are released via a direct outward budding and fission of plasma membrane blebs into the extracellular space to either facilitate virus propagation or regulate the immune responses. Moreover, EVs generated by virus-infected cells can incorporate virulence factors including viral protein and viral genetic material, and thus can resemble noninfectious viruses. Interactions of EVs with recipient cells have been shown to activate signaling pathways that may contribute to a sustained cellular response towards viral infections. EVs, by utilizing a complex set of cargos, can play a regulatory role in viral infection, both by facilitating and suppressing the infection. EV-based antiviral and antiretroviral drug delivery approaches provide an opportunity for targeted drug delivery. In this review, we summarize the literature on EVs, their associated involvement in transmission in viral infections, and potential therapeutic implications. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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18 pages, 3338 KiB  
Review
The Regulation of Flavivirus Infection by Hijacking Exosome-Mediated Cell–Cell Communication: New Insights on Virus–Host Interactions
by José Manuel Reyes-Ruiz, Juan Fidel Osuna-Ramos, Luis Adrián De Jesús-González, Selvin Noé Palacios-Rápalo, Carlos Daniel Cordero-Rivera, Carlos Noe Farfan-Morales, Arianna Mahely Hurtado-Monzón, Carla Elizabeth Gallardo-Flores, Sofía L. Alcaraz-Estrada, Juan Santiago Salas-Benito and Rosa María del Ángel
Viruses 2020, 12(7), 765; https://doi.org/10.3390/v12070765 - 16 Jul 2020
Cited by 21 | Viewed by 6117
Abstract
The arthropod-borne flaviviruses are important human pathogens, and a deeper understanding of the virus–host cell interaction is required to identify cellular targets that can be used as therapeutic candidates. It is well reported that the flaviviruses hijack several cellular functions, such as exosome-mediated [...] Read more.
The arthropod-borne flaviviruses are important human pathogens, and a deeper understanding of the virus–host cell interaction is required to identify cellular targets that can be used as therapeutic candidates. It is well reported that the flaviviruses hijack several cellular functions, such as exosome-mediated cell communication during infection, which is modulated by the delivery of the exosomal cargo of pro- or antiviral molecules to the receiving host cells. Therefore, to study the role of exosomes during flavivirus infections is essential, not only to understand its relevance in virus–host interaction, but also to identify molecular factors that may contribute to the development of new strategies to block these viral infections. This review explores the implications of exosomes in flavivirus dissemination and transmission from the vector to human host cells, as well as their involvement in the host immune response. The hypothesis about exosomes as a transplacental infection route of ZIKV and the paradox effect or the dual role of exosomes released during flavivirus infection are also discussed here. Although several studies have been performed in order to identify and characterize cellular and viral molecules released in exosomes, it is not clear how all of these components participate in viral pathogenesis. Further studies will determine the balance between protective and harmful exosomes secreted by flavivirus infected cells, the characteristics and components that distinguish them both, and how they could be a factor that determines the infection outcome. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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26 pages, 1206 KiB  
Review
Extracellular Vesicles in Viral Infections of the Nervous System
by Naseer A. Kutchy, Eric S. Peeples, Susmita Sil, Ke Liao, Ernest T. Chivero, Guoku Hu and Shilpa Buch
Viruses 2020, 12(7), 700; https://doi.org/10.3390/v12070700 - 28 Jun 2020
Cited by 27 | Viewed by 4756
Abstract
Almost all types of cells release extracellular vesicles (EVs) into the extracellular space. EVs such as exosomes and microvesicles are membrane-bound vesicles ranging in size from 30 to 1000 nm in diameter. Under normal conditions, EVs mediate cell to cell as well as [...] Read more.
Almost all types of cells release extracellular vesicles (EVs) into the extracellular space. EVs such as exosomes and microvesicles are membrane-bound vesicles ranging in size from 30 to 1000 nm in diameter. Under normal conditions, EVs mediate cell to cell as well as inter-organ communication via the shuttling of their cargoes which include RNA, DNA and proteins. Under pathological conditions, however, the number, size and content of EVs are found to be altered and have been shown to play crucial roles in disease progression. Emerging studies have demonstrated that EVs are involved in many aspects of viral infection-mediated neurodegenerative diseases. In the current review, we will describe the interactions between EV biogenesis and the release of virus particles while also reviewing the role of EVs in various viral infections, such as HIV-1, HTLV, Zika, CMV, EBV, Hepatitis B and C, JCV, and HSV-1. We will also discuss the potential uses of EVs and their cargoes as biomarkers and therapeutic vehicles for viral infections. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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19 pages, 1219 KiB  
Review
Extracellular Vesicles in Viral Spread and Antiviral Response
by Raquel Bello-Morales, Inés Ripa and José Antonio López-Guerrero
Viruses 2020, 12(6), 623; https://doi.org/10.3390/v12060623 - 8 Jun 2020
Cited by 47 | Viewed by 6658
Abstract
Viral spread by both enveloped and non-enveloped viruses may be mediated by extracellular vesicles (EVs), including microvesicles (MVs) and exosomes. These secreted vesicles have been demonstrated to be an efficient mechanism that viruses can use to enter host cells, enhance spread or evade [...] Read more.
Viral spread by both enveloped and non-enveloped viruses may be mediated by extracellular vesicles (EVs), including microvesicles (MVs) and exosomes. These secreted vesicles have been demonstrated to be an efficient mechanism that viruses can use to enter host cells, enhance spread or evade the host immune response. However, the complex interplay between viruses and EVs gives rise to antagonistic biological tasks—to benefit the viruses, enhancing infection and interfering with the immune system or to benefit the host, by mediating anti-viral responses. Exosomes from cells infected with herpes simplex type 1 (HSV-1) may transport viral and host transcripts, proteins and innate immune components. This virus may also use MVs to expand its tropism and evade the host immune response. This review aims to describe the current knowledge about EVs and their participation in viral infection, with a specific focus on the role of exosomes and MVs in herpesvirus infections, particularly that of HSV-1. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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17 pages, 2156 KiB  
Review
Evidence of the Mechanism by Which Polyomaviruses Exploit the Extracellular Vesicle Delivery System during Infection
by Simone Giannecchini
Viruses 2020, 12(6), 585; https://doi.org/10.3390/v12060585 - 27 May 2020
Cited by 17 | Viewed by 3554
Abstract
Increasing evidence suggests that human viruses can hijack extracellular vesicles (EVs) to deliver proteins, mRNAs, microRNAs (miRNAs) and whole viral particles during viral persistence in the host. Human polyomavirus (PyV) miRNAs, which downregulate large T-antigen expression and target host factors, help the virus [...] Read more.
Increasing evidence suggests that human viruses can hijack extracellular vesicles (EVs) to deliver proteins, mRNAs, microRNAs (miRNAs) and whole viral particles during viral persistence in the host. Human polyomavirus (PyV) miRNAs, which downregulate large T-antigen expression and target host factors, help the virus escape immune elimination and may have roles in the success of viral persistence/replication and the development of diseases. In this context, several investigations have detected PyV miRNAs in EVs obtained from cell culture supernatants after viral infection, demonstrating the ability of these vesicles to deliver miRNAs to uninfected cells, potentially counteracting new viral infection. Additionally, PyV miRNAs have been identified in EVs derived from the biological fluids of clinical samples obtained from patients with or at risk of severe PyV-associated diseases and from asymptomatic control healthy subjects. Interestingly, PyV miRNAs were found to be circulating in blood, urine, cerebrospinal fluid, and saliva samples from patients despite their PyV DNA status. Recently, the association between EVs and PyV viral particles was reported, demonstrating the ability of PyV viral particles to enter the cell without natural receptor-mediated entry and evade antibody-mediated neutralization or to be neutralized at a step different from that of the neutralization of naked whole viral particles. All these data point toward a potential role of the association between PyVs with EVs in viral persistence, suggesting that further work to define the implication of this interaction in viral reactivation is warranted. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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21 pages, 1887 KiB  
Review
Shedding Light on the Role of Extracellular Vesicles in HIV Infection and Wound Healing
by Aseel Alqatawni, Adhikarimayum Lakhikumar Sharma, Beatrice Attilus, Mudit Tyagi and Rene Daniel
Viruses 2020, 12(6), 584; https://doi.org/10.3390/v12060584 - 27 May 2020
Cited by 18 | Viewed by 4837
Abstract
Extracellular vesicles (EVs) play an important role in intercellular communication. They are naturally released from cells into the extracellular environment. Based on their biogenesis, release pathways, size, content, and function, EVs are classified into exosomes, microvesicles (MVs), and apoptotic bodies (ApoBDs). Previous research [...] Read more.
Extracellular vesicles (EVs) play an important role in intercellular communication. They are naturally released from cells into the extracellular environment. Based on their biogenesis, release pathways, size, content, and function, EVs are classified into exosomes, microvesicles (MVs), and apoptotic bodies (ApoBDs). Previous research has documented that EVs, specifically exosomes and MVs, play an important role in HIV infection, either by promoting HIV infection and pathogenesis or by inhibiting HIV-1 to a certain extent. We have also previously reported that EVs (particularly exosomes) from vaginal fluids inhibit HIV at the post-entry step (i.e., reverse transcription, integration). Besides the role that EVs play in HIV, they are also known to regulate the process of wound healing by regulating both the immune and inflammatory responses. It is noted that during the advanced stages of HIV infection, patients are at greater risk of wound-healing and wound-related complications. Despite ongoing research, the data on the actual effects of EVs in HIV infection and wound healing are still premature. This review aimed to update the current knowledge about the roles of EVs in regulating HIV pathogenesis and wound healing. Additionally, we highlighted several avenues of EV involvement in the process of wound healing, including coagulation, inflammation, proliferation, and extracellular matrix remodeling. Understanding the role of EVs in HIV infection and wound healing could significantly contribute to the development of new and potent antiviral therapeutic strategies and approaches to resolve impaired wounds in HIV patients. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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22 pages, 1644 KiB  
Review
The Role of Extracellular Vesicles as Allies of HIV, HCV and SARS Viruses
by Flavia Giannessi, Alessandra Aiello, Francesca Franchi, Zulema Antonia Percario and Elisabetta Affabris
Viruses 2020, 12(5), 571; https://doi.org/10.3390/v12050571 - 22 May 2020
Cited by 41 | Viewed by 14724
Abstract
Extracellular vesicles (EVs) are lipid bilayer-enclosed entities containing proteins and nucleic acids that mediate intercellular communication, in both physiological and pathological conditions. EVs resemble enveloped viruses in both structural and functional aspects. In full analogy with viral biogenesis, some of these vesicles are [...] Read more.
Extracellular vesicles (EVs) are lipid bilayer-enclosed entities containing proteins and nucleic acids that mediate intercellular communication, in both physiological and pathological conditions. EVs resemble enveloped viruses in both structural and functional aspects. In full analogy with viral biogenesis, some of these vesicles are generated inside cells and, once released into the extracellular milieu, are called “exosomes”. Others bud from the plasma membrane and are generally referred to as “microvesicles”. In this review, we will discuss the state of the art of the current studies on the relationship between EVs and viruses and their involvement in three important viral infections caused by HIV, HCV and Severe Acute Respiratory Syndrome (SARS) viruses. HIV and HCV are two well-known pathogens that hijack EVs content and release to create a suitable environment for viral infection. SARS viruses are a new entry in the world of EVs studies, but are equally important in this historical framework. A thorough knowledge of the involvement of the EVs in viral infections could be helpful for the development of new therapeutic strategies to counteract different pathogens. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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17 pages, 1015 KiB  
Brief Report
Expression Profiles of Exosomal MicroRNAs from HEV- and HCV-Infected Blood Donors and Patients: A Pilot Study
by Karen McGowan, Kenneth J. Simpson and Juraj Petrik
Viruses 2020, 12(8), 833; https://doi.org/10.3390/v12080833 - 30 Jul 2020
Cited by 15 | Viewed by 3236
Abstract
Exosomes seem to play an important role in hepatits C virus (HCV) and hepatitis E virus (HEV) infection by shielding their cargo from the host immune responses, with microRNAs being key exosomal components. Little is known about their involvement in a mixed HCV/HEV [...] Read more.
Exosomes seem to play an important role in hepatits C virus (HCV) and hepatitis E virus (HEV) infection by shielding their cargo from the host immune responses, with microRNAs being key exosomal components. Little is known about their involvement in a mixed HCV/HEV infection or at the early stages of infection, such as in asymptomatic blood donors (BDs). To obtain preliminary data, we have compared the exosomal microRNA expression profiles in four each of HCV RNA-positive, HEV RNA-positive and negative blood donors and four patients, one of whom was a rare patient with HCV/HEV co-infection. Exosomes were purified from sera by a combination of a precipitation and density gradient centrifugation and exosomal microRNA was analysed using Taqman array cards. Out of 33 deregulated miRNAs, miR-885-5p and miR-365 were upregulated in HCV BDs, miR-627-5p was downregulated in HCV BD and miR-221 was downregulated in HCV patients and BDs. In HEV infection, miR-526b appeared specifically downregulated. Six miRNAs (miR-628-3p, miR-194, miR-151-3p, miR-512-3p, miR-335 and miR-590) indicated a potential involvement in both infections. First time preliminary data on pre- and post-antiviral treatment exosomal microRNA profiles of the HEV/HCV co-infected patient revealed a pool of 77 upregulated and 43 downregulated miRNAs to be further investigated for their potential roles in these viral infections. Full article
(This article belongs to the Special Issue Viruses and Extracellular Vesicles)
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