Staufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein and Enhances Viral RNA Synthesis

ABSTRACT Ebola virus (EBOV) genome and mRNAs contain long, structured regions that could hijack host RNA-binding proteins to facilitate infection. We performed RNA affinity chromatography coupled with mass spectrometry to identify host proteins that bind to EBOV RNAs and identified four high-confide...

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Autores principales:	Jingru Fang, Colette Pietzsch, Palaniappan Ramanathan, Rodrigo I. Santos, Philipp A. Ilinykh, Mariano A. Garcia-Blanco, Alexander Bukreyev, Shelton S. Bradrick
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	RNA binding proteins RNA replication ebola virus virus-host interactions Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3e063c7ff21e4966a27fee9740480430
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spelling	oai:doaj.org-article:3e063c7ff21e4966a27fee97404804302021-11-15T15:58:20ZStaufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein and Enhances Viral RNA Synthesis10.1128/mBio.01771-182150-7511https://doaj.org/article/3e063c7ff21e4966a27fee97404804302018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01771-18https://doaj.org/toc/2150-7511ABSTRACT Ebola virus (EBOV) genome and mRNAs contain long, structured regions that could hijack host RNA-binding proteins to facilitate infection. We performed RNA affinity chromatography coupled with mass spectrometry to identify host proteins that bind to EBOV RNAs and identified four high-confidence proviral host factors, including Staufen1 (STAU1), which specifically binds both 3′ and 5′ extracistronic regions of the EBOV genome. We confirmed that EBOV infection rate and production of infectious particles were significantly reduced in STAU1-depleted cells. STAU1 was recruited to sites of EBOV RNA synthesis upon infection and enhanced viral RNA synthesis. Furthermore, STAU1 interacts with EBOV nucleoprotein (NP), virion protein 30 (VP30), and VP35; the latter two bridge the viral polymerase to the NP-coated genome, forming the viral ribonucleoprotein (RNP) complex. Our data indicate that STAU1 plays a critical role in EBOV replication by coordinating interactions between the viral genome and RNA synthesis machinery. IMPORTANCE Ebola virus (EBOV) is a negative-strand RNA virus with significant public health importance. Currently, no therapeutics are available for Ebola, which imposes an urgent need for a better understanding of EBOV biology. Here we dissected the virus-host interplay between EBOV and host RNA-binding proteins. We identified novel EBOV host factors, including Staufen1, which interacts with multiple viral factors and is required for efficient viral RNA synthesis.Jingru FangColette PietzschPalaniappan RamanathanRodrigo I. SantosPhilipp A. IlinykhMariano A. Garcia-BlancoAlexander BukreyevShelton S. BradrickAmerican Society for MicrobiologyarticleRNA binding proteinsRNA replicationebola virusvirus-host interactionsMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	RNA binding proteins RNA replication ebola virus virus-host interactions Microbiology QR1-502
spellingShingle	RNA binding proteins RNA replication ebola virus virus-host interactions Microbiology QR1-502 Jingru Fang Colette Pietzsch Palaniappan Ramanathan Rodrigo I. Santos Philipp A. Ilinykh Mariano A. Garcia-Blanco Alexander Bukreyev Shelton S. Bradrick Staufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein and Enhances Viral RNA Synthesis
description	ABSTRACT Ebola virus (EBOV) genome and mRNAs contain long, structured regions that could hijack host RNA-binding proteins to facilitate infection. We performed RNA affinity chromatography coupled with mass spectrometry to identify host proteins that bind to EBOV RNAs and identified four high-confidence proviral host factors, including Staufen1 (STAU1), which specifically binds both 3′ and 5′ extracistronic regions of the EBOV genome. We confirmed that EBOV infection rate and production of infectious particles were significantly reduced in STAU1-depleted cells. STAU1 was recruited to sites of EBOV RNA synthesis upon infection and enhanced viral RNA synthesis. Furthermore, STAU1 interacts with EBOV nucleoprotein (NP), virion protein 30 (VP30), and VP35; the latter two bridge the viral polymerase to the NP-coated genome, forming the viral ribonucleoprotein (RNP) complex. Our data indicate that STAU1 plays a critical role in EBOV replication by coordinating interactions between the viral genome and RNA synthesis machinery. IMPORTANCE Ebola virus (EBOV) is a negative-strand RNA virus with significant public health importance. Currently, no therapeutics are available for Ebola, which imposes an urgent need for a better understanding of EBOV biology. Here we dissected the virus-host interplay between EBOV and host RNA-binding proteins. We identified novel EBOV host factors, including Staufen1, which interacts with multiple viral factors and is required for efficient viral RNA synthesis.
format	article
author	Jingru Fang Colette Pietzsch Palaniappan Ramanathan Rodrigo I. Santos Philipp A. Ilinykh Mariano A. Garcia-Blanco Alexander Bukreyev Shelton S. Bradrick
author_facet	Jingru Fang Colette Pietzsch Palaniappan Ramanathan Rodrigo I. Santos Philipp A. Ilinykh Mariano A. Garcia-Blanco Alexander Bukreyev Shelton S. Bradrick
author_sort	Jingru Fang
title	Staufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein and Enhances Viral RNA Synthesis
title_short	Staufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein and Enhances Viral RNA Synthesis
title_full	Staufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein and Enhances Viral RNA Synthesis
title_fullStr	Staufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein and Enhances Viral RNA Synthesis
title_full_unstemmed	Staufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein and Enhances Viral RNA Synthesis
title_sort	staufen1 interacts with multiple components of the ebola virus ribonucleoprotein and enhances viral rna synthesis
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/3e063c7ff21e4966a27fee9740480430
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Staufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein and Enhances Viral RNA Synthesis

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