Neural stem cell-derived exosomes mediate viral entry

Brian Sims,1,2,* Linlin Gu,3,* Alexandre Krendelchtchikov,3 Qiana L Matthews3,4 1Division of Neonatology, Department of Pediatrics, 2Department of Cell, Developmental, and Integrative Biology, 3Division of Infectious Diseases, Department of Medicine, 4Center for AIDS Research, University of Alabam...

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Autores principales:	Sims B, Gu L, Krendelchtchikov A, Matthews QL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/332fcadfab33404ea087a624ccdd4b5f
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spelling	oai:doaj.org-article:332fcadfab33404ea087a624ccdd4b5f2021-12-02T02:01:33ZNeural stem cell-derived exosomes mediate viral entry1178-2013https://doaj.org/article/332fcadfab33404ea087a624ccdd4b5f2014-10-01T00:00:00Zhttp://www.dovepress.com/neural-stem-cell-derived-exosomes-mediate-viral-entry-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Brian Sims,1,2,* Linlin Gu,3,* Alexandre Krendelchtchikov,3 Qiana L Matthews3,4 1Division of Neonatology, Department of Pediatrics, 2Department of Cell, Developmental, and Integrative Biology, 3Division of Infectious Diseases, Department of Medicine, 4Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, USA *These authors contributed equally to this work Background: Viruses enter host cells through interactions of viral ligands with cellular receptors. Viruses can also enter cells in a receptor-independent fashion. Mechanisms regarding the receptor-independent viral entry into cells have not been fully elucidated. Exosomal trafficking between cells may offer a mechanism by which viruses can enter cells.Methods: To investigate the role of exosomes on cellular viral entry, we employed neural stem cell-derived exosomes and adenovirus type 5 (Ad5) for the proof-of-principle study. Results: Exosomes significantly enhanced Ad5 entry in Coxsackie virus and adenovirus receptor (CAR)-deficient cells, in which Ad5 only had very limited entry. The exosomes were shown to contain T-cell immunoglobulin mucin protein 4 (TIM-4), which binds phosphatidylserine. Treatment with anti-TIM-4 antibody significantly blocked the exosome-mediated Ad5 entry.Conclusion: Neural stem cell-derived exosomes mediated significant cellular entry of Ad5 in a receptor-independent fashion. This mediation may be hampered by an antibody specifically targeting TIM-4 on exosomes. This set of results will benefit further elucidation of virus/exosome pathways, which would contribute to reducing natural viral infection by developing therapeutic agents or vaccines. Keywords: neural stem cell-derived exosomes, adenovirus type 5, TIM-4, viral entry, phospholipidsSims BGu LKrendelchtchikov AMatthews QLDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 4893-4897 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Sims B Gu L Krendelchtchikov A Matthews QL Neural stem cell-derived exosomes mediate viral entry
description	Brian Sims,1,2,* Linlin Gu,3,* Alexandre Krendelchtchikov,3 Qiana L Matthews3,4 1Division of Neonatology, Department of Pediatrics, 2Department of Cell, Developmental, and Integrative Biology, 3Division of Infectious Diseases, Department of Medicine, 4Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, USA *These authors contributed equally to this work Background: Viruses enter host cells through interactions of viral ligands with cellular receptors. Viruses can also enter cells in a receptor-independent fashion. Mechanisms regarding the receptor-independent viral entry into cells have not been fully elucidated. Exosomal trafficking between cells may offer a mechanism by which viruses can enter cells.Methods: To investigate the role of exosomes on cellular viral entry, we employed neural stem cell-derived exosomes and adenovirus type 5 (Ad5) for the proof-of-principle study. Results: Exosomes significantly enhanced Ad5 entry in Coxsackie virus and adenovirus receptor (CAR)-deficient cells, in which Ad5 only had very limited entry. The exosomes were shown to contain T-cell immunoglobulin mucin protein 4 (TIM-4), which binds phosphatidylserine. Treatment with anti-TIM-4 antibody significantly blocked the exosome-mediated Ad5 entry.Conclusion: Neural stem cell-derived exosomes mediated significant cellular entry of Ad5 in a receptor-independent fashion. This mediation may be hampered by an antibody specifically targeting TIM-4 on exosomes. This set of results will benefit further elucidation of virus/exosome pathways, which would contribute to reducing natural viral infection by developing therapeutic agents or vaccines. Keywords: neural stem cell-derived exosomes, adenovirus type 5, TIM-4, viral entry, phospholipids
format	article
author	Sims B Gu L Krendelchtchikov A Matthews QL
author_facet	Sims B Gu L Krendelchtchikov A Matthews QL
author_sort	Sims B
title	Neural stem cell-derived exosomes mediate viral entry
title_short	Neural stem cell-derived exosomes mediate viral entry
title_full	Neural stem cell-derived exosomes mediate viral entry
title_fullStr	Neural stem cell-derived exosomes mediate viral entry
title_full_unstemmed	Neural stem cell-derived exosomes mediate viral entry
title_sort	neural stem cell-derived exosomes mediate viral entry
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/332fcadfab33404ea087a624ccdd4b5f
work_keys_str_mv	AT simsb neuralstemcellderivedexosomesmediateviralentry AT gul neuralstemcellderivedexosomesmediateviralentry AT krendelchtchikova neuralstemcellderivedexosomesmediateviralentry AT matthewsql neuralstemcellderivedexosomesmediateviralentry
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Neural stem cell-derived exosomes mediate viral entry

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