DENV inhibits type I IFN production in infected cells by cleaving human STING.

Dengue virus (DENV) is a pathogen with a high impact on human health. It replicates in a wide range of cells involved in the immune response. To efficiently infect humans, DENV must evade or inhibit fundamental elements of the innate immune system, namely the type I interferon response. DENV circumv...

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Autores principales:	Sebastian Aguirre, Ana M Maestre, Sarah Pagni, Jenish R Patel, Timothy Savage, Delia Gutman, Kevin Maringer, Dabeiba Bernal-Rubio, Reed S Shabman, Viviana Simon, Juan R Rodriguez-Madoz, Lubbertus C F Mulder, Glen N Barber, Ana Fernandez-Sesma
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/78139064b4bc4ba996ad45f43d5b6e8a
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spelling	oai:doaj.org-article:78139064b4bc4ba996ad45f43d5b6e8a2021-11-18T06:06:30ZDENV inhibits type I IFN production in infected cells by cleaving human STING.1553-73661553-737410.1371/journal.ppat.1002934https://doaj.org/article/78139064b4bc4ba996ad45f43d5b6e8a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23055924/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Dengue virus (DENV) is a pathogen with a high impact on human health. It replicates in a wide range of cells involved in the immune response. To efficiently infect humans, DENV must evade or inhibit fundamental elements of the innate immune system, namely the type I interferon response. DENV circumvents the host immune response by expressing proteins that antagonize the cellular innate immunity. We have recently documented the inhibition of type I IFN production by the proteolytic activity of DENV NS2B3 protease complex in human monocyte derived dendritic cells (MDDCs). In the present report we identify the human adaptor molecule STING as a target of the NS2B3 protease complex. We characterize the mechanism of inhibition of type I IFN production in primary human MDDCs by this viral factor. Using different human and mouse primary cells lacking STING, we show enhanced DENV replication. Conversely, mutated versions of STING that cannot be cleaved by the DENV NS2B3 protease induced higher levels of type I IFN after infection with DENV. Additionally, we show that DENV NS2B3 is not able to degrade the mouse version of STING, a phenomenon that severely restricts the replication of DENV in mouse cells, suggesting that STING plays a key role in the inhibition of DENV infection and spread in mice.Sebastian AguirreAna M MaestreSarah PagniJenish R PatelTimothy SavageDelia GutmanKevin MaringerDabeiba Bernal-RubioReed S ShabmanViviana SimonJuan R Rodriguez-MadozLubbertus C F MulderGlen N BarberAna Fernandez-SesmaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 10, p e1002934 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Sebastian Aguirre Ana M Maestre Sarah Pagni Jenish R Patel Timothy Savage Delia Gutman Kevin Maringer Dabeiba Bernal-Rubio Reed S Shabman Viviana Simon Juan R Rodriguez-Madoz Lubbertus C F Mulder Glen N Barber Ana Fernandez-Sesma DENV inhibits type I IFN production in infected cells by cleaving human STING.
description	Dengue virus (DENV) is a pathogen with a high impact on human health. It replicates in a wide range of cells involved in the immune response. To efficiently infect humans, DENV must evade or inhibit fundamental elements of the innate immune system, namely the type I interferon response. DENV circumvents the host immune response by expressing proteins that antagonize the cellular innate immunity. We have recently documented the inhibition of type I IFN production by the proteolytic activity of DENV NS2B3 protease complex in human monocyte derived dendritic cells (MDDCs). In the present report we identify the human adaptor molecule STING as a target of the NS2B3 protease complex. We characterize the mechanism of inhibition of type I IFN production in primary human MDDCs by this viral factor. Using different human and mouse primary cells lacking STING, we show enhanced DENV replication. Conversely, mutated versions of STING that cannot be cleaved by the DENV NS2B3 protease induced higher levels of type I IFN after infection with DENV. Additionally, we show that DENV NS2B3 is not able to degrade the mouse version of STING, a phenomenon that severely restricts the replication of DENV in mouse cells, suggesting that STING plays a key role in the inhibition of DENV infection and spread in mice.
format	article
author	Sebastian Aguirre Ana M Maestre Sarah Pagni Jenish R Patel Timothy Savage Delia Gutman Kevin Maringer Dabeiba Bernal-Rubio Reed S Shabman Viviana Simon Juan R Rodriguez-Madoz Lubbertus C F Mulder Glen N Barber Ana Fernandez-Sesma
author_facet	Sebastian Aguirre Ana M Maestre Sarah Pagni Jenish R Patel Timothy Savage Delia Gutman Kevin Maringer Dabeiba Bernal-Rubio Reed S Shabman Viviana Simon Juan R Rodriguez-Madoz Lubbertus C F Mulder Glen N Barber Ana Fernandez-Sesma
author_sort	Sebastian Aguirre
title	DENV inhibits type I IFN production in infected cells by cleaving human STING.
title_short	DENV inhibits type I IFN production in infected cells by cleaving human STING.
title_full	DENV inhibits type I IFN production in infected cells by cleaving human STING.
title_fullStr	DENV inhibits type I IFN production in infected cells by cleaving human STING.
title_full_unstemmed	DENV inhibits type I IFN production in infected cells by cleaving human STING.
title_sort	denv inhibits type i ifn production in infected cells by cleaving human sting.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/78139064b4bc4ba996ad45f43d5b6e8a
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DENV inhibits type I IFN production in infected cells by cleaving human STING.

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