DDX56 Binds to Chikungunya Virus RNA To Control Infection

ABSTRACT DEAD box RNA helicases regulate diverse facets of RNA biology. Proteins of this family carry out essential cellular functions, and emerging literature is revealing additional roles in immune defense. Using RNA interference screening, we identified an evolutionarily conserved antiviral role...

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Autores principales:	Frances Taschuk, Iulia Tapescu, Ryan H. Moy, Sara Cherry
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	alphavirus chikungunya Sindbis CLIP-Seq DEAD-box helicase RNAi Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fb1b308235c64fa58e29343a11925644
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spelling	oai:doaj.org-article:fb1b308235c64fa58e29343a119256442021-11-15T16:19:07ZDDX56 Binds to Chikungunya Virus RNA To Control Infection10.1128/mBio.02623-202150-7511https://doaj.org/article/fb1b308235c64fa58e29343a119256442020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02623-20https://doaj.org/toc/2150-7511ABSTRACT DEAD box RNA helicases regulate diverse facets of RNA biology. Proteins of this family carry out essential cellular functions, and emerging literature is revealing additional roles in immune defense. Using RNA interference screening, we identified an evolutionarily conserved antiviral role for the helicase DDX56 against the alphavirus Sindbis virus (SINV), a mosquito-transmitted pathogen that infects humans. Depletion of DDX56 enhanced infection in Drosophila and human cells. Furthermore, we found that DDX56 also controls the emerging alphavirus chikungunya virus (CHIKV) through an interferon-independent mechanism. Using cross-linking immunoprecipitation (CLIP-Seq), we identified a predicted stem-loop on the viral genomic RNA bound by DDX56. Mechanistically, we found that DDX56 levels increase in the cytoplasm during CHIKV infection. In the cytoplasm, DDX56 impacts the earliest step in the viral replication cycle by binding and destabilizing the incoming viral genomic RNA, thereby attenuating infection. Thus, DDX56 is a conserved antiviral RNA binding protein that controls alphavirus infection. IMPORTANCE Arthropod-borne viruses are diverse pathogens and include the emerging virus chikungunya virus, which is associated with human disease. Through genetic screening, we found that the conserved RNA binding protein DDX56 is antiviral against chikungunya virus in insects and humans. DDX56 relocalizes from the nucleus to the cytoplasm, where it binds to a stem-loop in the viral genome and destabilizes incoming genomes. Thus, DDX56 is an evolutionarily conserved antiviral factor that controls alphavirus infection.Frances TaschukIulia TapescuRyan H. MoySara CherryAmerican Society for MicrobiologyarticlealphaviruschikungunyaSindbisCLIP-SeqDEAD-box helicaseRNAiMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	alphavirus chikungunya Sindbis CLIP-Seq DEAD-box helicase RNAi Microbiology QR1-502
spellingShingle	alphavirus chikungunya Sindbis CLIP-Seq DEAD-box helicase RNAi Microbiology QR1-502 Frances Taschuk Iulia Tapescu Ryan H. Moy Sara Cherry DDX56 Binds to Chikungunya Virus RNA To Control Infection
description	ABSTRACT DEAD box RNA helicases regulate diverse facets of RNA biology. Proteins of this family carry out essential cellular functions, and emerging literature is revealing additional roles in immune defense. Using RNA interference screening, we identified an evolutionarily conserved antiviral role for the helicase DDX56 against the alphavirus Sindbis virus (SINV), a mosquito-transmitted pathogen that infects humans. Depletion of DDX56 enhanced infection in Drosophila and human cells. Furthermore, we found that DDX56 also controls the emerging alphavirus chikungunya virus (CHIKV) through an interferon-independent mechanism. Using cross-linking immunoprecipitation (CLIP-Seq), we identified a predicted stem-loop on the viral genomic RNA bound by DDX56. Mechanistically, we found that DDX56 levels increase in the cytoplasm during CHIKV infection. In the cytoplasm, DDX56 impacts the earliest step in the viral replication cycle by binding and destabilizing the incoming viral genomic RNA, thereby attenuating infection. Thus, DDX56 is a conserved antiviral RNA binding protein that controls alphavirus infection. IMPORTANCE Arthropod-borne viruses are diverse pathogens and include the emerging virus chikungunya virus, which is associated with human disease. Through genetic screening, we found that the conserved RNA binding protein DDX56 is antiviral against chikungunya virus in insects and humans. DDX56 relocalizes from the nucleus to the cytoplasm, where it binds to a stem-loop in the viral genome and destabilizes incoming genomes. Thus, DDX56 is an evolutionarily conserved antiviral factor that controls alphavirus infection.
format	article
author	Frances Taschuk Iulia Tapescu Ryan H. Moy Sara Cherry
author_facet	Frances Taschuk Iulia Tapescu Ryan H. Moy Sara Cherry
author_sort	Frances Taschuk
title	DDX56 Binds to Chikungunya Virus RNA To Control Infection
title_short	DDX56 Binds to Chikungunya Virus RNA To Control Infection
title_full	DDX56 Binds to Chikungunya Virus RNA To Control Infection
title_fullStr	DDX56 Binds to Chikungunya Virus RNA To Control Infection
title_full_unstemmed	DDX56 Binds to Chikungunya Virus RNA To Control Infection
title_sort	ddx56 binds to chikungunya virus rna to control infection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/fb1b308235c64fa58e29343a11925644
work_keys_str_mv	AT francestaschuk ddx56bindstochikungunyavirusrnatocontrolinfection AT iuliatapescu ddx56bindstochikungunyavirusrnatocontrolinfection AT ryanhmoy ddx56bindstochikungunyavirusrnatocontrolinfection AT saracherry ddx56bindstochikungunyavirusrnatocontrolinfection
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DDX56 Binds to Chikungunya Virus RNA To Control Infection

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