MiR-199a Inhibits Secondary Envelopment of Herpes Simplex Virus-1 Through the Downregulation of Cdc42-specific GTPase Activating Protein Localized in Golgi Apparatus

Abstract Because several studies have shown that exogenous miR-199a has antiviral effects against various viruses, including herpesviruses, we examined how miR-199a exerts its antiviral effects using epithelial tumour cell lines infected with herpes simplex virus-1 (HSV-1). We found that both miR-19...

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Autores principales:	Kyousuke Kobayashi, Fumiko Suemasa, Hiroshi Sagara, Shinya Nakamura, Yasushi Ino, Kazuyoshi Kobayashi, Hiroaki Hiramatsu, Takeshi Haraguchi, Kazuo Kurokawa, Tomoki Todo, Akihiko Nakano, Hideo Iba
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d9bb1c64cd046da89e4bf87ba1e65f7
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spelling	oai:doaj.org-article:5d9bb1c64cd046da89e4bf87ba1e65f72021-12-02T16:06:09ZMiR-199a Inhibits Secondary Envelopment of Herpes Simplex Virus-1 Through the Downregulation of Cdc42-specific GTPase Activating Protein Localized in Golgi Apparatus10.1038/s41598-017-06754-32045-2322https://doaj.org/article/5d9bb1c64cd046da89e4bf87ba1e65f72017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06754-3https://doaj.org/toc/2045-2322Abstract Because several studies have shown that exogenous miR-199a has antiviral effects against various viruses, including herpesviruses, we examined how miR-199a exerts its antiviral effects using epithelial tumour cell lines infected with herpes simplex virus-1 (HSV-1). We found that both miR-199a-5p and -3p impair the secondary envelopment of HSV-1 by suppressing their common target, ARHGAP21, a Golgi-localized GTPase-activating protein for Cdc42. We further found that the trans-cisternae of the Golgi apparatus are a potential membrane compartment for secondary envelopment. Exogenous expression of either pre-miR-199a or sh-ARHGAP21 exhibited shared phenotypes i.e. alteration of Golgi function in uninfected cells, inhibition of HSV-1 secondary envelopment, and reduction of trans-Golgi proteins upon HSV-1 infection. A constitutively active form of Cdc42 also inhibited HSV-1 secondary envelopment. Endogenous levels of miR-199a in epithelial tumour cell lines were negatively correlated with the efficiency of HSV-1 secondary envelopment within these cells. These results suggest that miR-199a is a crucial regulator of Cdc42 activity on Golgi membranes, which is important for the maintenance of Golgi function and for the secondary envelopment of HSV-1 upon its infection.Kyousuke KobayashiFumiko SuemasaHiroshi SagaraShinya NakamuraYasushi InoKazuyoshi KobayashiHiroaki HiramatsuTakeshi HaraguchiKazuo KurokawaTomoki TodoAkihiko NakanoHideo IbaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kyousuke Kobayashi Fumiko Suemasa Hiroshi Sagara Shinya Nakamura Yasushi Ino Kazuyoshi Kobayashi Hiroaki Hiramatsu Takeshi Haraguchi Kazuo Kurokawa Tomoki Todo Akihiko Nakano Hideo Iba MiR-199a Inhibits Secondary Envelopment of Herpes Simplex Virus-1 Through the Downregulation of Cdc42-specific GTPase Activating Protein Localized in Golgi Apparatus
description	Abstract Because several studies have shown that exogenous miR-199a has antiviral effects against various viruses, including herpesviruses, we examined how miR-199a exerts its antiviral effects using epithelial tumour cell lines infected with herpes simplex virus-1 (HSV-1). We found that both miR-199a-5p and -3p impair the secondary envelopment of HSV-1 by suppressing their common target, ARHGAP21, a Golgi-localized GTPase-activating protein for Cdc42. We further found that the trans-cisternae of the Golgi apparatus are a potential membrane compartment for secondary envelopment. Exogenous expression of either pre-miR-199a or sh-ARHGAP21 exhibited shared phenotypes i.e. alteration of Golgi function in uninfected cells, inhibition of HSV-1 secondary envelopment, and reduction of trans-Golgi proteins upon HSV-1 infection. A constitutively active form of Cdc42 also inhibited HSV-1 secondary envelopment. Endogenous levels of miR-199a in epithelial tumour cell lines were negatively correlated with the efficiency of HSV-1 secondary envelopment within these cells. These results suggest that miR-199a is a crucial regulator of Cdc42 activity on Golgi membranes, which is important for the maintenance of Golgi function and for the secondary envelopment of HSV-1 upon its infection.
format	article
author	Kyousuke Kobayashi Fumiko Suemasa Hiroshi Sagara Shinya Nakamura Yasushi Ino Kazuyoshi Kobayashi Hiroaki Hiramatsu Takeshi Haraguchi Kazuo Kurokawa Tomoki Todo Akihiko Nakano Hideo Iba
author_facet	Kyousuke Kobayashi Fumiko Suemasa Hiroshi Sagara Shinya Nakamura Yasushi Ino Kazuyoshi Kobayashi Hiroaki Hiramatsu Takeshi Haraguchi Kazuo Kurokawa Tomoki Todo Akihiko Nakano Hideo Iba
author_sort	Kyousuke Kobayashi
title	MiR-199a Inhibits Secondary Envelopment of Herpes Simplex Virus-1 Through the Downregulation of Cdc42-specific GTPase Activating Protein Localized in Golgi Apparatus
title_short	MiR-199a Inhibits Secondary Envelopment of Herpes Simplex Virus-1 Through the Downregulation of Cdc42-specific GTPase Activating Protein Localized in Golgi Apparatus
title_full	MiR-199a Inhibits Secondary Envelopment of Herpes Simplex Virus-1 Through the Downregulation of Cdc42-specific GTPase Activating Protein Localized in Golgi Apparatus
title_fullStr	MiR-199a Inhibits Secondary Envelopment of Herpes Simplex Virus-1 Through the Downregulation of Cdc42-specific GTPase Activating Protein Localized in Golgi Apparatus
title_full_unstemmed	MiR-199a Inhibits Secondary Envelopment of Herpes Simplex Virus-1 Through the Downregulation of Cdc42-specific GTPase Activating Protein Localized in Golgi Apparatus
title_sort	mir-199a inhibits secondary envelopment of herpes simplex virus-1 through the downregulation of cdc42-specific gtpase activating protein localized in golgi apparatus
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5d9bb1c64cd046da89e4bf87ba1e65f7
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MiR-199a Inhibits Secondary Envelopment of Herpes Simplex Virus-1 Through the Downregulation of Cdc42-specific GTPase Activating Protein Localized in Golgi Apparatus

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