Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking

Abstract Chikungunya virus (CHIKV) is an emerging arbovirus of the Togaviridae family that poses a present worldwide threat to human in the absence of any licensed vaccine or antiviral treatment to control viral infection. Here, we show that compounds interfering with intracellular cholesterol trans...

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Autores principales:	Sineewanlaya Wichit, Rodolphe Hamel, Eric Bernard, Loïc Talignani, Fodé Diop, Pauline Ferraris, Florian Liegeois, Peeraya Ekchariyawat, Natthanej Luplertlop, Pornapat Surasombatpattana, Frédéric Thomas, Andres Merits, Valérie Choumet, Pierre Roques, Hans Yssel, Laurence Briant, Dorothée Missé
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1c070191521a479fbd9e7c290c814112
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spelling	oai:doaj.org-article:1c070191521a479fbd9e7c290c8141122021-12-02T12:30:17ZImipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking10.1038/s41598-017-03316-52045-2322https://doaj.org/article/1c070191521a479fbd9e7c290c8141122017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03316-5https://doaj.org/toc/2045-2322Abstract Chikungunya virus (CHIKV) is an emerging arbovirus of the Togaviridae family that poses a present worldwide threat to human in the absence of any licensed vaccine or antiviral treatment to control viral infection. Here, we show that compounds interfering with intracellular cholesterol transport have the capacity to inhibit CHIKV replication in human skin fibroblasts, a major viral entry site in the human host. Pretreatment of these cells with the class II cationic amphiphilic compound U18666A, or treatment with the FDA-approved antidepressant drug imipramine resulted in a near total inhibition of viral replication and production at the highest concentration used without any cytotoxic effects. Imipramine was found to affect both the fusion and replication steps of the viral life cycle. The key contribution of cholesterol availability to the CHIKV life cycle was validated further by the use of fibroblasts from Niemann-Pick type C (NPC) patients in which the virus was unable to replicate. Interestingly, imipramine also strongly inhibited the replication of several Flaviviridae family members, including Zika, West Nile and Dengue virus. Together, these data show that this compound is a potential drug candidate for anti-arboviral treatment.Sineewanlaya WichitRodolphe HamelEric BernardLoïc TalignaniFodé DiopPauline FerrarisFlorian LiegeoisPeeraya EkchariyawatNatthanej LuplertlopPornapat SurasombatpattanaFrédéric ThomasAndres MeritsValérie ChoumetPierre RoquesHans YsselLaurence BriantDorothée MisséNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sineewanlaya Wichit Rodolphe Hamel Eric Bernard Loïc Talignani Fodé Diop Pauline Ferraris Florian Liegeois Peeraya Ekchariyawat Natthanej Luplertlop Pornapat Surasombatpattana Frédéric Thomas Andres Merits Valérie Choumet Pierre Roques Hans Yssel Laurence Briant Dorothée Missé Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking
description	Abstract Chikungunya virus (CHIKV) is an emerging arbovirus of the Togaviridae family that poses a present worldwide threat to human in the absence of any licensed vaccine or antiviral treatment to control viral infection. Here, we show that compounds interfering with intracellular cholesterol transport have the capacity to inhibit CHIKV replication in human skin fibroblasts, a major viral entry site in the human host. Pretreatment of these cells with the class II cationic amphiphilic compound U18666A, or treatment with the FDA-approved antidepressant drug imipramine resulted in a near total inhibition of viral replication and production at the highest concentration used without any cytotoxic effects. Imipramine was found to affect both the fusion and replication steps of the viral life cycle. The key contribution of cholesterol availability to the CHIKV life cycle was validated further by the use of fibroblasts from Niemann-Pick type C (NPC) patients in which the virus was unable to replicate. Interestingly, imipramine also strongly inhibited the replication of several Flaviviridae family members, including Zika, West Nile and Dengue virus. Together, these data show that this compound is a potential drug candidate for anti-arboviral treatment.
format	article
author	Sineewanlaya Wichit Rodolphe Hamel Eric Bernard Loïc Talignani Fodé Diop Pauline Ferraris Florian Liegeois Peeraya Ekchariyawat Natthanej Luplertlop Pornapat Surasombatpattana Frédéric Thomas Andres Merits Valérie Choumet Pierre Roques Hans Yssel Laurence Briant Dorothée Missé
author_facet	Sineewanlaya Wichit Rodolphe Hamel Eric Bernard Loïc Talignani Fodé Diop Pauline Ferraris Florian Liegeois Peeraya Ekchariyawat Natthanej Luplertlop Pornapat Surasombatpattana Frédéric Thomas Andres Merits Valérie Choumet Pierre Roques Hans Yssel Laurence Briant Dorothée Missé
author_sort	Sineewanlaya Wichit
title	Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking
title_short	Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking
title_full	Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking
title_fullStr	Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking
title_full_unstemmed	Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking
title_sort	imipramine inhibits chikungunya virus replication in human skin fibroblasts through interference with intracellular cholesterol trafficking
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1c070191521a479fbd9e7c290c814112
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Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking

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