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      The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application

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          Abstract

          Eukaryotic cells produce extracellular vesicles (EVs) mediating intercellular communication. These vesicles encompass many bio-molecules such as proteins, nucleic acids, and lipids that are transported between cells and regulate pathophysiological actions in the recipient cell. Exosomes originate from multivesicular bodies inside cells and microvesicles shed from the plasma membrane and participate in various pathological conditions. Retroviruses such as Human Immunodeficiency Virus -type 1 (HIV-1) and Human T-cell leukemia virus (HTLV)-1 engage exosomes for spreading and infection. Exosomes from virus-infected cells transfer viral components such as miRNAs and proteins that promote infection and inflammation. Additionally, these exosomes deliver virus receptors to target cells that make them susceptible to virus entry. HIV-1 infected cells release exosomes that contribute to the pathogenesis including neurological disorders and malignancy. Exosomes can also potentially carry out as a modern approach for the development of HIV-1 and HTLV-1 vaccines. Furthermore, as exosomes are present in most biological fluids, they hold the supreme capacity for clinical usage in the early diagnosis and prognosis of viral infection and associated diseases. Our current knowledge of exosomes' role from virus-infected cells may provide an avenue for efficient retroviruses associated with disease prevention. However, the exact mechanism involved in retroviruses infection/ inflammation remains elusive and related exosomes research will shed light on the mechanisms of pathogenesis.

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          Most cited references131

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          Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

          ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
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            Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness

            Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.
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              Shedding light on the cell biology of extracellular vesicles

              Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
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                Author and article information

                Contributors
                fkashanc@gmu.edu
                Jafari.reza@umsu.ac.ir
                Journal
                Cell Biosci
                Cell Biosci
                Cell & Bioscience
                BioMed Central (London )
                2045-3701
                15 January 2021
                15 January 2021
                2021
                : 11
                : 19
                Affiliations
                [1 ]GRID grid.412763.5, ISNI 0000 0004 0442 8645, Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, , Urmia University of Medical Sciences, ; Shafa St, Ershad Blvd., P.O. Box: 1138, 57147 Urmia, Iran
                [2 ]GRID grid.412888.f, ISNI 0000 0001 2174 8913, Immunology Research Center, , Tabriz University of Medical Sciences, ; Tabriz, Iran
                [3 ]GRID grid.412888.f, ISNI 0000 0001 2174 8913, Department of Immunology, Faculty of Medicine, , Tabriz University of Medical Sciences, ; Tabriz, Iran
                [4 ]GRID grid.412888.f, ISNI 0000 0001 2174 8913, Tuberculosis and Lung Diseases Research Center, , Tabriz University of Medical Sciences, ; Tabriz, Iran
                [5 ]GRID grid.412763.5, ISNI 0000 0004 0442 8645, Department of Pharmacology and Toxicology, School of Pharmacy, , Urmia University of Medical Sciences, ; Urmia, Iran
                [6 ]GRID grid.22448.38, ISNI 0000 0004 1936 8032, School of Systems Biology, Laboratory of Molecular Virology, , George Mason University, ; Discovery Hall Room 182, 10900 University Blvd., Manassas, VA 20110 USA
                Author information
                http://orcid.org/0000-0003-2036-9043
                Article
                537
                10.1186/s13578-021-00537-0
                7810184
                33451365
                3e44cded-cfab-44b7-ac92-4110f1807f09
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 12 October 2020
                : 9 January 2021
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Cell biology
                exosomes,extracellular vesicles,hiv-1,htlv-1,retroviruses
                Cell biology
                exosomes, extracellular vesicles, hiv-1, htlv-1, retroviruses

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