Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells

Brian Sims,1–3,* Anitra L Farrow,4,* Sparkle D Williams,1,2 Anju Bansal,4 Alexandre Krendelchtchikov,1,2,4 Linlin Gu,5 Qiana L Matthews3,4,6 1Division of Neonatology, Department of Pediatrics, 2Department of Cell, Developmental and Integrative Biology, 3Center for AIDS Research, 4Division...

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Autores principales:	Sims B, Farrow AL, Williams SD, Bansal A, Krendelchtchikov A, Gu L, Matthews QL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Exosomes human immunodeficiency virus 1 T cell immunoglobulin and mucin proteins phosphatidylserine nanoparticle tracking analysis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d8f16581439744e593cec8e6f8aef794
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spelling	oai:doaj.org-article:d8f16581439744e593cec8e6f8aef7942021-12-02T00:38:48ZRole of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells1178-2013https://doaj.org/article/d8f16581439744e593cec8e6f8aef7942017-07-01T00:00:00Zhttps://www.dovepress.com/role-of-tim-4-in-exosome-dependent-entry-of-hiv-1-into-human-immune-ce-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Brian Sims,1–3,* Anitra L Farrow,4,* Sparkle D Williams,1,2 Anju Bansal,4 Alexandre Krendelchtchikov,1,2,4 Linlin Gu,5 Qiana L Matthews3,4,6 1Division of Neonatology, Department of Pediatrics, 2Department of Cell, Developmental and Integrative Biology, 3Center for AIDS Research, 4Division of Infectious Diseases, 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, 6Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL, USA *These authors contributed equally to this work Abstract: Exosomes, 30–200 nm nanostructures secreted from donor cells and internalized by recipient cells, can play an important role in the cellular entry of some viruses. These microvesicles are actively secreted into various body fluids, including blood, urine, saliva, cerebrospinal fluid, and breast milk. We successfully isolated exosomes from human breast milk and plasma. The size and concentration of purified exosomes were measured by nanoparticle tracking, while Western blotting confirmed the presence of the exosomal-associated proteins CD9 and CD63, clathrin, and T cell immunoglobulin and mucin proteins (TIMs). Through viral infection assays, we determined that HIV-1 utilizes an exosome-dependent mechanism for entry into human immune cells. The virus contains high amounts of phosphatidylserine (PtdSer) and may bind PtdSer receptors, such as TIMs. This mechanism is supported by our findings that exosomes from multiple sources increased HIV-1 entry into T cells and macrophages, and viral entry was potently blocked with anti-TIM-4 antibodies. Keywords: exosomes, HIV-1, T cell immunoglobulin and mucin proteins, phosphatidylserine, nanoparticle tracking analysisSims BFarrow ALWilliams SDBansal AKrendelchtchikov AGu LMatthews QLDove Medical PressarticleExosomeshuman immunodeficiency virus 1T cell immunoglobulin and mucin proteinsphosphatidylserinenanoparticle tracking analysisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4823-4833 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Exosomes human immunodeficiency virus 1 T cell immunoglobulin and mucin proteins phosphatidylserine nanoparticle tracking analysis Medicine (General) R5-920
spellingShingle	Exosomes human immunodeficiency virus 1 T cell immunoglobulin and mucin proteins phosphatidylserine nanoparticle tracking analysis Medicine (General) R5-920 Sims B Farrow AL Williams SD Bansal A Krendelchtchikov A Gu L Matthews QL Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells
description	Brian Sims,1–3,* Anitra L Farrow,4,* Sparkle D Williams,1,2 Anju Bansal,4 Alexandre Krendelchtchikov,1,2,4 Linlin Gu,5 Qiana L Matthews3,4,6 1Division of Neonatology, Department of Pediatrics, 2Department of Cell, Developmental and Integrative Biology, 3Center for AIDS Research, 4Division of Infectious Diseases, 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, 6Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL, USA *These authors contributed equally to this work Abstract: Exosomes, 30–200 nm nanostructures secreted from donor cells and internalized by recipient cells, can play an important role in the cellular entry of some viruses. These microvesicles are actively secreted into various body fluids, including blood, urine, saliva, cerebrospinal fluid, and breast milk. We successfully isolated exosomes from human breast milk and plasma. The size and concentration of purified exosomes were measured by nanoparticle tracking, while Western blotting confirmed the presence of the exosomal-associated proteins CD9 and CD63, clathrin, and T cell immunoglobulin and mucin proteins (TIMs). Through viral infection assays, we determined that HIV-1 utilizes an exosome-dependent mechanism for entry into human immune cells. The virus contains high amounts of phosphatidylserine (PtdSer) and may bind PtdSer receptors, such as TIMs. This mechanism is supported by our findings that exosomes from multiple sources increased HIV-1 entry into T cells and macrophages, and viral entry was potently blocked with anti-TIM-4 antibodies. Keywords: exosomes, HIV-1, T cell immunoglobulin and mucin proteins, phosphatidylserine, nanoparticle tracking analysis
format	article
author	Sims B Farrow AL Williams SD Bansal A Krendelchtchikov A Gu L Matthews QL
author_facet	Sims B Farrow AL Williams SD Bansal A Krendelchtchikov A Gu L Matthews QL
author_sort	Sims B
title	Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells
title_short	Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells
title_full	Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells
title_fullStr	Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells
title_full_unstemmed	Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells
title_sort	role of tim-4 in exosome-dependent entry of hiv-1 into human immune cells
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/d8f16581439744e593cec8e6f8aef794
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Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells

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